全文获取类型
收费全文 | 3427篇 |
免费 | 205篇 |
国内免费 | 1篇 |
出版年
2024年 | 6篇 |
2023年 | 30篇 |
2022年 | 58篇 |
2021年 | 125篇 |
2020年 | 81篇 |
2019年 | 91篇 |
2018年 | 112篇 |
2017年 | 92篇 |
2016年 | 123篇 |
2015年 | 202篇 |
2014年 | 194篇 |
2013年 | 261篇 |
2012年 | 286篇 |
2011年 | 273篇 |
2010年 | 173篇 |
2009年 | 140篇 |
2008年 | 168篇 |
2007年 | 197篇 |
2006年 | 187篇 |
2005年 | 156篇 |
2004年 | 155篇 |
2003年 | 121篇 |
2002年 | 110篇 |
2001年 | 30篇 |
2000年 | 23篇 |
1999年 | 25篇 |
1998年 | 29篇 |
1997年 | 20篇 |
1996年 | 16篇 |
1995年 | 11篇 |
1994年 | 12篇 |
1993年 | 14篇 |
1992年 | 8篇 |
1991年 | 14篇 |
1990年 | 6篇 |
1989年 | 13篇 |
1988年 | 8篇 |
1987年 | 8篇 |
1985年 | 7篇 |
1984年 | 4篇 |
1982年 | 4篇 |
1978年 | 6篇 |
1977年 | 4篇 |
1975年 | 4篇 |
1974年 | 3篇 |
1973年 | 4篇 |
1972年 | 3篇 |
1971年 | 3篇 |
1970年 | 2篇 |
1968年 | 2篇 |
排序方式: 共有3633条查询结果,搜索用时 31 毫秒
1.
2.
3.
Teresa K. Aman Bruce A. Maki Thomas J. Ruffino Eileen M. Kasperek Gabriela K. Popescu 《The Journal of biological chemistry》2014,289(27):18805-18817
Protein kinase A (PKA) enhances synaptic plasticity in the central nervous system by increasing NMDA receptor current amplitude and Ca2+ flux in an isoform-dependent yet poorly understood manner. PKA phosphorylates multiple residues on GluN1, GluN2A, and GluN2B subunits in vivo, but the functional significance of this multiplicity is unknown. We examined gating and permeation properties of recombinant NMDA receptor isoforms and of receptors with altered C-terminal domain (CTDs) prior to and after pharmacological inhibition of PKA. We found that PKA inhibition decreased GluN1/GluN2B but not GluN1/GluN2A gating; this effect was due to slower rates for receptor activation and resensitization and was mediated exclusively by the GluN2B CTD. In contrast, PKA inhibition reduced NMDA receptor-relative Ca2+ permeability (PCa/PNa) regardless of the GluN2 isoform and required the GluN1 CTD; this effect was due primarily to decreased unitary Ca2+ conductance, because neither Na+ conductance nor Ca2+-dependent block was altered substantially. Finally, we show that both the gating and permeation effects can be reproduced by changing the phosphorylation state of a single residue: GluN2B Ser-1166 and GluN1 Ser-897, respectively. We conclude that PKA effects on NMDA receptor gating and Ca2+ permeability rely on distinct phosphorylation sites located on the CTD of GluN2B and GluN1 subunits. This separate control of NMDA receptor properties by PKA may account for the specific effects of PKA on plasticity during synaptic development and may lead to drugs targeted to alter NMDA receptor gating or Ca2+ permeability. 相似文献
4.
The concentration of opiate receptors in the brains of mice was determined by means of a naloxone-binding assay. The strains of mice used in these experiments were C57BL/6By, BALB/cBy, their reciprocal F1 hybrids, and 7 recombinant-inbred strains derived by inbreeding from the F2 generation. These strains could be divided into 3 groups on the basis of the number of opiate receptors: high (CXBH); low (CXBK); and intermediate (all the other strains). The difference in stereospecific binding of naloxone reflects a difference in the total number of receptor sites rather than in the affinity for the drug. The recombinantinbred strains also differ in their analgesic response to morphine, as previously determined by the tail-flick assay. The differences in the number of opiate receptors are not enough to account for the genetic difference in analgesic responsiveness. Both these parameters appear to be under different genetic control, and at least 2 genetic determinants may be involved in regulating the level of opiate receptors. 相似文献
5.
Anton Pauw Sunshine A. Van Bael Halton A. Peters Steven D. Allison José L. C. Camargo Miguel Cifuentes-Jara Aurlstela Conserva Teresa Garcia Restom Tamara Heartsill-Scalley Scott A. Mangan Gabriela Nunez-lturri Elsie Rivera-Ocasio Mark Rountree Susanne Vetter Carolina Volkmer de Castllho 《Biotropica》2004,36(3):410-413
6.
Evidence for negative regulation of T cell growth by low affinity interleukin 2 receptors 总被引:2,自引:0,他引:2
A Kumar J L Moreau D Baran J Thèze 《Journal of immunology (Baltimore, Md. : 1950)》1987,138(5):1485-1493
Two experimental situations have been studied, and the results provide evidence for a negative regulatory role for the low affinity interleukin 2 receptor (LA-IL 2R). The IL 2-dependent T helper cell line L-14, deprived of IL 2, becomes quiescent and expresses comparable numbers of high affinity IL 2R (HA-IL 2R) and LA-IL 2R. After activation by recombinant IL 2, this cell line preferentially expresses LA-IL 2R. The IL 2 responsiveness of the L-14 cell line was found to vary according to the ratio of LA-IL 2R to HA-IL 2R: the relative predominance of the LA-IL 2R coincides with a hyporeactivity of cells to IL 2. In contrast, a predominance of HA-IL 2R is accompanied by an increase in cellular IL 2 reactivity. Treatment of three IL 2-dependent T cell lines (L-14, HT-2, and C30.1) with limited amounts of recombinant IL 2 and moderate concentrations of anti-IL 2R monoclonal antibodies stimulates T cell growth. This treatment was shown to selectively diminish the expression of membrane LA-IL 2R. The stimulation was attributed to the decrease of expression of LA-IL 2R. 相似文献
7.
Gabriela VizÁrovÁ 《Biologia Plantarum》1987,29(3):230-233
The cultivars of barley and wheat resistant to mildew had a higher level of free zeatin and its derivatives during the whole
ontogeny than the susceptible cultivars. The effect of exogenous application of cytokinins on the growth ofErysiphe graminis DC. was different. Kinetin and benzylaminopurine showed only a slight inhibitory effect. Zeatin and its derivatives completely
inhibited growth of this fungus.
Presented at the International Symposium “Plant Growth Regulators” held on June 18-22 1984 at Liblice, Czechoslovakia. 相似文献
8.
Unusual sequence element found at the end of an amplicon. 总被引:17,自引:1,他引:16
In a polyomavirus-transformed rat cell line, designated LPT, the polyomavirus DNA is integrated into a single chromosomal site. Treatment of LPT cells with carcinogens induces amplification of the integrated virus DNA and flanking cellular sequences. We show that the amplification is arrested within a specific cell DNA segment that maps 1.3 to 1.85 kilobases beyond one virus-cell DNA junction, defined as the left junction. We also present the sequence of an 897-base-pair fragment spanning the arrest site. This fragment contains an unusual sequence element, which consists of two contiguous components, a potential cruciform with stems of 6 base pairs and a d(G-A)27 X d(T-C)27 tract, and maps 1,497 to 1,564 nucleotides beyond the left junction. The possibility that this unusual sequence plays a role in the arrest of the amplification process is discussed. 相似文献
9.
Aleš Vančura Ivana Vančurová Jan Kopecký Jaroslav Maršálek Daniel Cikánek Gabriela Basařová Vladimir Křišťan 《Archives of microbiology》1989,151(6):537-540
Synthesis of threonine dehydratase in Streptomyces fradiae was positively influenced by valine and negatively by isoleucine. However, these two amino acids had no effect on the activity of this enzyme. Synthesis of threonine dehydratase in -aminobutyrate resistant mutants of S. fradiae was pronouncedly less sensitive to the positive effect of valine and this change in regulation led to valine overproduction. Synthesis of acetohydroxy acid synthase is regulated in a similar manner to that of threonine dehydratase, however a lower level of expression was detected in -aminobutyrate resistant mutants. And again, no effect of branched-chain amino acids on acetohydroxy acid synthase activity was observed. It follows that in S. fradiae synthesis of threonine dehydratase is the main regulatory mechanism governing production and the mutual ratio of synthesized valine and isoleucine.Abbreviations -AB
-aminobutyrate
- AHAS
acetohydroxy acid synthase
- -KB
-ketobutyrate
- MNNG
N-methyl-N-nitro-N-nitrosoguanidine
- TD
threonine dehydratase
- Trans. B.
transaminase of branched-chain amino acids
- VDH
valine dehydrogenase 相似文献
10.
Characterization of the soluble murine IL-2R and estimation of its affinity for IL-2 总被引:1,自引:0,他引:1
IL-2 induces cells of the cytotoxic T cell line C30.1 to express large numbers of membrane IL-2R (mIL-2R). At the height of activation, these cells also release a soluble form of IL-2R (sIL-2R). Using either crude supernatant or a semi-purified preparation of sIL-2R obtained by affinity chromatography, studies were performed to characterize murine sIL-2R. Its m.w. was determined by both gel filtration and SDS-PAGE. The affinity of sIL-2R for a panel of mAb known to recognize different epitopes of mIL-2R (p55 subunit) was assessed by saturation and competition experiments. The relationship between the various epitopes was studied by cross-inhibition experiments. The data suggest that sIL-2R and mIL-2R (p55 subunit) are structurally similar. The ability of sIL-2R to bind IL-2 was assessed by measuring the dissociation and the inhibition constant of the molecule for IL-2. Both values coincide and indicate that the affinity of sIL-2R for IL-2 is at least 10-fold lower than the that of low affinity mIL-2R. The biologic implications of these findings are discussed. 相似文献