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21.
Single-cell analysis by flow cytometry has enabled us to analyze the effects of a phorbol ester and known tumour promoter, TPA, on the phenotypes of four tumour lines. TPA is capable of triggering a variety of cellular alterations that can affect gene expression and the biochemical balance of intracellular events. We have investigated the effect of TPA on such properties as rate of proliferation, differentiation, expression of cell surface molecules, and susceptibility to natural killer (NK) cell-mediated cytolysis. Four human leukemia and lymphoma cell lines; K562, MOLT 4, Raji, and HL60, were studied in their response to TPA treatment. Based on measurements of the defined cellular properties, we have characterized the pleiotropic responses of each tumour cell line to the phorbol ester in relation to intensity and time of onset of each response. The effects of TPA are highly varied, ranging in time of onset from minutes to days, and in intensity from strong to weak within the four cell lines studied. However, within all the processes that are affected, the activation of protein kinase C appears to be a common initiating event of phorbol ester induction. 相似文献
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In the past year, much has been learned about structure-function correlations in the tubulin molecule, and specifically about the nature and roles of post-translational modifications and tubulin isotypes. The interactions between tubulin and its ligands--both microtubule-associated proteins and anti-mitotic drugs--are becoming clearer at the molecular level. 相似文献
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R Deka A P Reddy B N Mukherjee B M Das S Banerjee M Roy B Dey K C Malhotra H Walter 《Human heredity》1988,38(5):261-266
Previous studies have reported a high incidence of hemoglobin E (HbE) in Northeast Indian populations. In the present study 10 endogamous populations of Assam belonging to two racial groups, Caucasoid and Mongoloid, were examined. The frequency of HbE gene (Hb beta E) in the Caucasoid caste populations is around 0.1, whereas the gene is highly prevalent in the Mongoloid populations, frequencies ranging between 0.2 and 0.6. Predominance of Hb beta E in the Tibeto-Burman speakers is contrary to observations made in Southeast Asia, where an association between Austro-Asiatic speakers and high prevalence of HbE exist. The highest occurrence of the gene in this area, which is on the far end of the proposed centre of distribution in Northern Kampuchea and Northeast Thailand, is also a deviation from the expected pattern of gene distribution. It is speculated that Hb beta E in the Tibeto-Burman populations of Assam arose by an independent mutation which contributed to the high frequencies of Hb beta E in the Northeast Indian populations. 相似文献
26.
Retinoic acid inhibits phospholipid turnover and protein kinase C activity in RA-sensitive but not in RA-resistant cells 总被引:2,自引:0,他引:2
Treatment with 10(-5) M retinoic acid causes loss of anchorage-independent growth in src-transformed RR1022 cells but not in ras-transformed KNRK cells. In an effort to elucidate the mechanisms underlying this difference, we investigated the effect of RA on phospholipid turnover and PKC activity in these two cell lines. 10(-5) M RA treatment caused a drastic inhibition of 32P incorporation into PI and PA and a large increase in 32P incorporation into PC in RR1022 cells. Similar treatment of KNRK cells yielded no change in PC or PA labelling and a much smaller decrease in PI labelling. Furthermore, 10(-5) M RA treatment causes a large decrease in PKC activity in RR1022 cells (35% of control) but only a small decrease in KNRK cells (78% of control). We suggest that these effects are part of an altered signal transduction pathway which mediates the differential effects of RA on anchorage-independent growth in these two cell lines. 相似文献
27.
Cobalamin-dependent methionine synthase (5-methyltetrahydrofolate-homocysteine methyltransferase, EC 2.1.1.13) has been isolated from Escherichia coli B in homogeneous form. The enzyme is isolated in an inactive form with the visible absorbance properties of cob(II)alamin. The inactive enzyme exhibits an electron paramagnetic resonance (EPR) spectrum at 38 K that is characteristic of cob(II)alamin at acid pH, where the protonated dimethylbenzimidazole substituent is not coordinated with the cobalt nucleus (base-off cobalamin). An additional, variable component of the EPR spectrum of the inactive enzyme has the characteristics of a cob(III)alamin-superoxide complex. Previous work by others [Taylor, R.T., & Weissbach, H. (1969) Arch. Biochem. Biophys. 129, 745-766. Fujii, K., & Huennekens, F.M. (1979) in Biochemical Aspects of Nutrition (Yagi, K., Ed.) pp 173-183, Japan Scientific Societies, Tokyo] has demonstrated that the enzyme can be activated by reductive methylation using adenosylmethionine as the methyl donor. We present data indicating that the conversion of inactive to methylated enzyme is correlated with the disappearance of the EPR spectrum as expected for the conversion of paramagnetic cob(II)alamin to diamagnetic methylcobalamin. When the methyl group is transferred from the methylated enzyme to homocysteine under aerobic conditions, cob(II)alamin/cob(III)alamin-superoxide enzyme is regenerated as indicated by the return of the visible absorbance properties of the initially isolated enzyme and partial return of the EPR spectrum. Our enzyme preparations contain copper in approximately 1:1 stoichiometry with cobalt as determined by atomic absorption spectroscopy.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
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Human skin fibroblasts actively elongate a portion of incorporated C20 polyunsaturated fatty acids to their respective C22 derivatives. As much as 40% of incorporated [14C]eicosapentaenoate is elongated within 8 h and 85% by 48 h. Elongation of [14C]arachidonate is initially less than half that of [14C]eicosapentaenoate and plateaus at 20-30% of incorporated 14C-labeled fatty acid. The elongation of 5,8,11-[14C]eicosatrienoate is intermediate between that of 20:4(n-6) and 20:5(n-3). Docosatetraenoate is not an effective inhibitor of the elongation of arachidonate, thus suggesting that the observed plateau is not due to product inhibition. When concentrations of exogenous fatty acids are increased, these cells elongate substantial quantities of C20 polyunsaturated fatty acids; elongation of eicosapentaenoate is consistently more extensive than that of arachidonate. Eicosapentaenoate is also an effective inhibitor of the elongation of [14C]arachidonate. Increases in exogenous arachidonate up to 10 microM result in an increase in elongation of [14C]arachidonate both in absolute quantities and as a percentage of that incorporated; the arachidonate thus acts as a positive modulator of its own elongation. Increased eicosapentaenoate also enhances the elongation of [14C]eicosapentaenoate, but only at lower concentrations (0.02-0.15 microM). The factors which regulate the elongation of C20 polyunsaturated fatty acids in human skin fibroblasts serve to permit extensive elongation of eicosapentaenoate while retaining incorporated arachidonate primarily in its C20 form. 相似文献
30.
D. Banerjee R. J. W. Pentney I. Chackalaparampil B. B. Mukherjee 《Experimental cell research》1986,166(2):442-454
Anchorage-independent growth in vitro is strongly correlated with cellular malignancy in vivo and it has been shown that retinoic acid (RA; a vitamin A analog) inhibits anchorage-independent growth of a wide variety of oncogenically transformed cells (RA-sensitive cells). We report here that decreased or lack of phosphorylation of a group of low molecular weight (20-30 kD) cell surface membrane proteins, particularly one of Mr 28 kD, correlates strongly with RA-induced loss of anchorage-independent growth of RA-sensitive cells. Our studies also show that this group of proteins are not phosphorylated in non-transformed cells which do not grow in an anchorage-independent manner. Analysis of [35S]methionine-labeled proteins revealed that these polypeptides are present in both RA-treated and untreated cell surface membranes. This suggests that modulation of phosphorylation rather than lack of synthesis of these proteins is correlated with anchorage regulation of cells. V8 protease mapping of the 28 kD phosphoprotein from transformed cells, irrespective of their origin or of transforming agents, revealed complete fragment homology. Furthermore, the 28 kD phosphoprotein was found to be phosphorylated exclusively at threonine residues. The data obtained from this study suggest that the ability of cells to grow without anchorage is correlated with the phosphorylation of a group of cell surface membrane proteins and RA inhibits anchorage-independent growth by interfering with the phosphorylation rather than synthesis of these proteins. 相似文献