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91.
92.
Amrita A. Nagle Fei-Fei Gan Gavin Jones Choon-Leng So Geoffrey Wells Eng-Hui Chew 《PloS one》2012,7(11)
Multifunctional trans-cinnamaldehyde (CA) and its analogs display anti-cancer properties, with 2-benzoyloxycinnamaldehyde (BCA) and 5-fluoro-2-hydroxycinnamaldehyde (FHCA) being identified as the ortho-substituted analogs that possess potent anti-tumor activities. In this study, BCA, FHCA and a novel analog 5-fluoro-2-benzoyloxycinnamaldehyde (FBCA), were demonstrated to decrease growth and colony formation of human colon-derived HCT 116 and mammary-derived MCF-7 carcinoma cells under non-adhesive conditions. The 2-benzoyloxy and 5-fluoro substituents rendered FBCA more potent than BCA and equipotent to FHCA. The cellular events by which these cinnamaldehydes caused G2/M phase arrest and halted proliferation of HCT 116 cells were thereby investigated. Lack of significant accumulation of mitosis marker phospho-histone H3 in cinnamaldehyde-treated cells indicated that the analogs arrested cells in G2 phase. G2 arrest was brought about partly by cinnamaldehyde-mediated depletion of cell cycle proteins involved in regulating G2 to M transition and spindle assembly, namely cdk1, cdc25C, mad2, cdc20 and survivin. Cyclin B1 levels were found to be increased, which in the absence of active cdk1, would fail to drive cells into M phase. Concentrations of cinnamaldehydes that brought about dysregulation of levels of cell cycle proteins also caused tubulin aggregation, as evident from immunodetection of dose-dependent tubulin accumulation in the insoluble cell lysate fractions. In a cell-free system, reduced biotin-conjugated iodoacetamide (BIAM) labeling of tubulin protein pretreated with cinnamaldehydes was indicative of drug interaction with the sulfhydryl groups in tubulin. In conclusion, cinnamaldehydes treatment at proapoptotic concentrations caused tubulin aggregation and dysegulation of cell cycle regulatory proteins cdk1 and cdc25C that contributed at least in part to arresting cells at G2 phase, resulting in apoptotic cell death characterized by emergence of cleaved forms of caspase 3 and poly (ADP-ribose) polymerase (PARP). Results presented in this study have thus provided further insights into the intricate network of cellular events by which cinnamaldehydes induce tumor cell death. 相似文献
93.
C S Chew 《Biochimica et biophysica acta》1985,846(3):370-378
The role of extracellular calcium in the action of the secretagogues, carbachol, histamine and forskolin, on parietal cell HCl secretion was investigated using glands isolated from rabbit gastric mucosa. Omission of calcium from the cellular incubation medium and chelation of a major portion of contaminating calcium with EGTA resulted in a disappearance of the initial transient response to carbachol (as measured by uptake of the weak base, amino[14C]pyrine), but the sustained response to carbachol persisted. Neither histamine nor forskolin-stimulated increase in amino[14C]pyrine uptake were affected by omission of extracellular calcium. Furthermore, the potentiating interactions between histamine and carbachol and between forskolin and carbachol appeared to occur independent of extracellular calcium. Attempts to assess the contribution of intracellular calcium to secretory activity using the Ca2+ antagonists, verapamil, nifedipine, nicardipine and lanthanum, and the putative intracellular Ca2+ antogonist, TMB-8 (3,4,5-trimethyloxybenzoic acid 8-(diethyl-amino)-octyl ester) were unsuccessful. Nifedipine had no effect on secretagogue stimulated amino[14C]pyrine accumulation even at concentration well above the pA2 reported for excitable tissues. Verapamil, nicardipine, lanthanum and TMB-8 all appeared to have nonspecific inhibitory effects on amino [14C]pyrine uptake. From these results we conclude that: (1) parietal cell HCl secretion can occur independent of extracellular Ca2+; (2) influx of extracellular Ca2+ enhances the response to carbachol but has little influence on the secretory response initiated by cAMP-dependent secretagogues; and (3) parietal cell Ca2+ channels have a different molecular configuration than Ca2+ channels in excitable cells. 相似文献
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Histone and casein kinases of lactating bovine mammary gland 总被引:1,自引:0,他引:1
98.
Lei Li Ryan Z.L. Lim Lawrence S.U. Lee Nicholas S.Y. Chew 《Biochimica et Biophysica Acta (BBA)/General Subjects》2018,1862(8):1790-1800
Background
HIV infection and/or the direct pathogenic effects of circulating HIV proteins impairs the physiological function of mesenchymal stem cells (MSCs), and contribute to the pathogenesis of age-related clinical comorbidities in people living with HIV. The SDF-1/CXCR4 pathway is vital for modulating MSC proliferation, migration and differentiation. HIV glycoprotein gp120 inhibits SDF-1 induced chemotaxis by downregulating the expression and function of CXCR4 in monocytes, B and T cells. The influence of gp120 on CXCR4 expression and migration in MSCs is unknown.Methods
We investigated CXCR4 expression and SDF-1/CXCR4-mediated MSC migration in response to gp120, and its effect on downstream signaling pathways: focal adhesion kinase (FAK)/Paxillin and extracellular signal-regulated kinase (ERK).Results
Gp120 upregulated MSC CXCR4 expression. This potentiated the effects of SDF-1 in inducing chemotaxis; FAK/Paxillin and ERK pathways were over-activated, thereby facilitating actin stress fiber reorganization. CXCR4 blockage or depletion abrogated the observed effects.Conclusion
Gp120 from both T- and M- tropic HIV strains upregulated CXCR4 expression in MSCs, resulting in enhanced MSC chemotaxis in response to SDF-1.General significance
HIV infection and its proteins are known to disrupt physiological differentiation of MSC; increased gp120-driven migration amplifies the total MSC population destined for ineffective and inappropriate differentiation, thus contributing to the pathogenesis of HIV-related comorbidities. Additionally, given that MSCs are permissive to HIV infection, initial cellular priming by gp120 results in increased expression of CXCR4 and could lead to co-receptor switching and cell tropism changes in chronic HIV infection and may have implications against CCR5-knockout based HIV cure strategies. 相似文献99.
OBJECTIVE: The Singapore Breast Screening Pilot Project (SBSPP) was embarked upon (1994-1997) to determine if mammography was useful in early breast cancer detection among Asian women. PATIENTS AND MEASUREMENTS: Of 28 231 women screened, fine needle aspiration cytology (FNAC) was performed in 232 individuals as part of the triple assessment. RESULTS: Absolute and complete sensitivities for the diagnosis of carcinoma were 46.7% and 82.2%, respectively, based on the results of FNAC. Specificity was 63.3%. The inadequate rate was 31%. Five women who were considered cancer-free on triple assessment and, in two cases open diagnostic biopsy during the SBSPP, subsequently developed breast cancer after a median follow-up of 6 years. CONCLUSION: Although our FNAC results compared relatively well with international standards, they reflect a small cohort, and may face additional difficulties in a larger programme. 相似文献
100.