[1]  Nicholson L K,  Lindon J C, Holmes E. 'Metabonomics':  understanding the metabolic responses of living systems to pathophysiological stimuli via multivariate statistical analysis of biological NMR spectroscopic data[J]. Xenobiotica, 1999,  29(2): 1 181-1 189.

[2]  Nicholson J K,  Connelly J,  Lindon J C, et al. Metabonomics:  a platform for studying drug toxicity and gene function[J]. Nat Rev Drug Disc, 2002, 1(2): 153-161.

[3]  Oliver, S. Guilt-by-association goes global[J]. Nature，2000,  403:  601-603.

[4]  Thomas，GH. Metabolomics breaks the silence[J]. Trends Microbiol. 2001，9(4): 158.

[5]  Fiehn O. Metabolomics the link between genotypes and phenotypes[J]. Plant Mol Biol. 2002，48(1-2): 155-171.

[6]  Choi H K, Choi Y H,  Verberne M, et al. Metabolic fingerprinting of wild type and transgenic tobacco plants by (1)H NMR and multivariate analysis technique[J]. Phytochemistry. 2004,  65(7): 857-864. 

[7]  Ketchum R E,  Rithner C D,  Qiu D,  et al. Taxus metabolomics:  methyl jasmonate preferentially induces production of taxoids oxygenated at C-13 in Taxus x media cell cultures[J]. Phytochemistry. 2003,  62(6): 901-909. 

[8]  Fiehn O. Metabolic networks of Cucurbita maxima phloem[J]. Phytochemistry. 2003,  62(6): 875-886. 

[9]  Fiehn O,  Kopka J,  Dormann P，et al. Metabolite profiling for plant functional genomics[J]. Nat Biotechnol. 2000,  18(11): 1 157-1 161.

[10]  Bruder E D,  Lee P C,  Raff H. Metabolomic analysis of adrenal lipids during hypoxia in the neonatal rat:  implications in steroidogenesis[J]. Am J Physiol-Endoc Metab. 2004, 286(5): E697-703. 

[11]  Griffin J L,  Cemal C K,  Pook M A. Defining a metabolic phenotype in the brain of a transgenic mouse model of spinocerebellar ataxia 3
[J]. Physiol Genomics. 2004, 13; 16(3): 334-340.

[12]  Sullards M C,  Wang E,  Peng Q, et al. Metabolomic profiling of sphingolipids in human glioma cell lines by liquid chromatography tandem mass spectrometry[J]. Cell Mol Biol (Noisy-le-grand). 2003,  49(5): 789-797. 

[13]  Marin S,  Chiang K,  Bassilian S, et al. Metabolic strategy of boar spermatozoa revealed by a metabolomic characterization[J]. FEBS Lett. 2003,  554(3): 342-346. 

[14]  Griffiths J R,  Stubbs M. Opportunities for studying cancer by metabolomics:  preliminary observations on tumors deficient in hypoxiainducible factor 1[J]. Adv Enzyme Regul. 2003,  43: 67-76. 

[15]  Plumb R S,  Stumpf C L,  Granger J H,  et al. Use of liquid chromatography/time of flight mass spectrometry and multivariate statistical analysis shows promise for the detection of drug metabolites in biological fluids[J]. Rapid Commun Mass Spectrom. 2003，17(23): 2 632-2 638. 

[16]  Pham-Tuan H,  Kaskavelis L,  Daykin C A,  et al. Method development in high-performance liquid chromatography for high-throughput profiling and metabonomic studies of biofluid samples[J]. J Chromatogr B: Analyt Technol Biomed Life Sci. 2003，789(2): 283-301. 

[17]  Plumb R S, Stumpf C L, Gorenstein M V, et al. Metabonomics:  the use of electrospray mass spectrometry coupled to reversed-phase liquid chromatography shows potential for the screening of rat urine in drug development[J]. Rapid Commun Mass Spectrom. 2002，16(20): 1 991-1 996. 

[18]  Bales J R,  Higham D P, Howe I, et al. Use of high resolution proton nuclear magnetic resonance spectroscopy for rapid multicomponent analysis of urine[J]. Clin Chem,  1984,  30(2):  426-432.

[19]  Nicholson  J K,  Wilson,  I D. Prog Nucl Mag Res Spectrosc. 1989,  21:  449-501. 

[20]  Tang H,  Wang Y,  Nicholson J K, et al. Use of relaxationedited onedimensional and two dimensional nuclear magnetic resonance spectroscopy to improve detection of small metabolites in blood plasma[J]. Anal Biochem. 2004,  325(2): 260-272. 

[21]  Van Q N,  Chmurny G N,  Veenstra T D.The depletion of protein signals in metabonomics analysis with the WET-CPMG pulse sequence[J]. Biochem Bioph Res Commun. 2003，301(4): 952-959.

[22]  Beckwith-Hall B M,  Thompson N A, Nicholson J K, et al. A metabonomic investigation of hepatotoxicity using diffusion-edited ¹H NMR spectroscopy of blood serum[J]. Analyst. 2003，128(7): 814-818. 

[23]  Wang Y, Bollard M E, Keun H, et al. Spectral editing and pattern recognition methods applied to high-resolution magic-angle spinning ¹H nuclear magnetic resonance spectroscopy of liver tissues[J]. Anal Biochem. 2003,  323(1): 26-32. 

[24]  Griffin J L. Metabonomics: NMR spectroscopy and pattern recognition analysis of body fluids and tissues for characterisation of xenobiotic toxicity and disease diagnosis[J]. Curr Opin Chem Biol. 2003. 7(5): 648-654.

[25]  Lindon J C,  Holmes E,  Nicholson J K. Pattern recognition methods and applications in biomedical magnetic resonance[J]. Prog Nucl Mag Res Spectrosc, 2001,  39(1):  1-40.

[26]  Holmes E. Identification of novel biomarkers of renal toxicity using automatic data reduction techniques and PCA of proton NMR spectra of urine[J]. Chemometr Intell Lab Syst, 1998,  44(11): 251-261.

[27]  BeckwithHall B M,  Brindle J T,  Barton R H,  et al. Application of orthogonal signal correction to minimise the effects of physical and biological variation in high resolution ¹H NMR spectra of biofluids[J]. Analyst. 2002, 127(10): 1 283-1 288. 

[28]  Gavaghan C L,  Wilson I D,  Nicholson J K. Physiological variation in metabolic phenotyping and functional genomic studies:  use of orthogonal signal correction and PLS-DA[J]. FEBS Lett. 2002,  530(1-3): 191-196. 

[29]  Holmes E,  Antti H. Chemometric contributions to the evolution of metabonomics: mathematical solutions to characterising and interpreting complex biological NMR spectra[J]. Analyst. 2002 Dec; 127(12): 1 549-1 557.

[30]  Shockcor J P,  Holmes E. Metabonomic applications in toxicity screening and disease diagnosis[J]. Curr Top Med Chem, 2002, 2(1):  35-51.

[31]  Kacser H. Recent developments beyond metabolic control analysis[J]. Biochem Soc Trans, 1993, 23(3):  387-391.

[32]  Daykin C A, Foxall P J, Connor S C, et al. The comparison of plasma deproteinization methods for the detection of low-molecularweight metabolites by ¹H nuclear magnetic resonance spectroscopy[J]. Anal Biochem, 2002,  304(10): 220-230.

[33]  Beckwith-Hall B M, Nicholson J K, Nicholls A W, et al. Nuclear magnetic resonance spectroscopy and principal components analysis investigations into biochemical effect of three model hepatotoxins[J]. Chem Res Toxicol,  1998,  11(2):  260-272.

[34]  Waters N J, Holmes E,  Williams A, et al. NMR and pattern recognition studies on the time-related metabolic effects of alphanaphthylisothiocyanate on liver,  urine,  and plasma in the rat:  an integrative metabonomic approach[J]. Chem Res Toxicol. 2001,  14(10): 1 401-1 412. 

[35]  Nicholls A W,  Holmes E,  Lindon J C, et al. Metabonomic investigations into hydrazine toxicity in the rat[J]. Chem Res Toxicol. 2001,  14(8): 975-987. 

[36]  Coen M,  Lenz E M,  Nicholson J K, et al.  An integrated metabonomic investigation of acetaminophen toxicity in the mouse using NMR spectroscopy[J]. Chem Res Toxicol. 2003, 16(3): 295-303. 

[37]  Coen M,  Ruepp S U,  Lindon J C,  et al. Integrated application of transcriptomics and metabonomics yields new insight into the toxicity due to paracetamol in the mouse[J]. J Pharm Biomed Anal. 2004, 35(1): 93-105.

[38]  Slim R M,  Robertson D G,  Albassam M, et al.  Effect of dexamethasone on the metabonomics profile associated with phosphodiesterase inhibitor-induced vascular lesions in rats[J]. Toxicol Appl Pharm. 2002, 183(2): 108-109. 

[39]  王全军，颜贤忠，吴纯启, 等. Z24经口染毒大鼠血浆的代谢组学研究[J]. 卫生毒理学杂志，已接受. 

[40]  Raamsdonk L M，Teusink B,  Broadhurst  D，et al. A functional genomics strategy that uses metabolome data to reveal the phenptype of silent mutations[J]. Nat Biotech,  2001, 19(3): 45-50.

[41]  Gavaghan C L,  Holmes E, Lenz E,  et al. An NMR-based metabonomics approach to investigate the biochemical consequences of genetic strain differences;  application to the C57BL10J and Alpk: Apfcd mouse[J]. FEBS Lett,  2000, 484(10):  169-174.

[42]  Griffin J L,  Walker L A,  Garrod S, et al. NMR spectroscopy based metabonomic studies on the comparative biochemistry of the kidney and urine of the bank vole (Clethrionomys glareolus ),  wood mouse (Apodemus sylvaticus ),  white toothed shrew (Crocidura suaveolens ) and the laboratory rat[J]. Comp Biochem. Phys B: Biochem Mol Biol, 2000, 127:  357-367.

[43]  Holmes E,  Nicholson J K,  Tranter G. Metabonomic characterization of genetic variations in toxicological and metabolic responses using probabilistic neural networks[J]. Chem Res Toxicol. 2001，14(2): 182-191.

[44]  Griffin J L,  Williams H J,  Sang E, et al.  Metabolic profiling of genetic disorders: a multitissue ¹H nuclear magnetic resonance spectroscopic and pattern recognition study into dystrophic tissue[J]. Anal Biochem. 2001，293(1): 16-21. 

[45]  Nicholls  A W,  Mortishire-Smith R J, Nicholson  J K. NMR spectroscopic-based metabonomic studies of urinary metabolite variation in acclimatizing germ-free rats[J]. Chem Res Toxicol,  2003, 16: 1 395-1 404.

[46]  Bollard M E, Holmes E, Lindon J C, et al.  Investigations into biochemical changes due to diurnal variation and estrus cycle in female rats using high-resolution (1)H NMR spectroscopy of urine and pattern recognition[J]. Anal Biochem. 2001,  295(2): 194-202. 

[47]  Brindle J T,  Nicholson J K,  Schofield P M, et al. Application of chemometrics to \{\}\+1H NMR spectroscopic data to investigate a relationship between human serum metabolic profiles and hypertension[J]. Analyst. 2003，128(1): 32-36. 

[48]  Moolenaar S H, Engelke U F,  Wevers R A. Proton nuclear magnetic resonance spectroscopy of body fluids in the field of inborn errors of metabolism[J]. Ann Clin Biochem. 2003，40(1): 16-24. 

[49]  Brindle J T,  Antti H,  Holmes E ，et al. Rapid and noninvasive diagnosis of the presence and severity of coronary heart disease using ¹H NMR based metabonomics[J]. Nat Med, 2002，8(12): 1 439-1 444. 

[50]  Robertson D G,  Reily M D,  Albassam M, et al. Metabonomic assessment of vasculitis in rats[J]. Cardiovasc Toxicol. 2001，1(1): 7-19.

[51]  Eisen M B,  Spellman P T,  Brown P O, et al. Cluster analysis and display of genome-wide expression patterns[J]. Proc Natl Acad Sci USA, 1998,  95(25):  14 863-14 868

[52]  Geisow M. Proteomics:  one small step for a digital computer,  one giant leap for humankind[J]. Nat Biotech, 1998, 16(2):  206-207.

[53]  Holmes E,  Nicholls A W,  Lindon J C, et al.  Chemometric models for toxicity classification based on NMR spectra of biofluids[J]. Chem Res Toxicol, 2000, 13(11):  471-478.

[54]  Griffin J L,  Williams H J,  Sang E，et al. Metabolic profiling of genetic disorders:  a multi-tissues ¹H NMR spectroscopic and pattern recognition study into dystrophic tissue[J]. Anal Biochem, 2001, 293(9):  16-21.

[55]  Button KJ,  Everett J R,  Newman M J, et al. On-line liquid chromatography coupled with high field NMR and mass spectrometry (LC-NMR-MS):  A new technique for drug metabolite structure elucidation[J]. J Pharm Biomed Anal, 1997,  15(8): 1 903-1 912.