全文获取类型
收费全文 | 3047篇 |
免费 | 329篇 |
国内免费 | 7篇 |
出版年
2022年 | 33篇 |
2021年 | 51篇 |
2020年 | 20篇 |
2019年 | 39篇 |
2018年 | 32篇 |
2017年 | 22篇 |
2016年 | 69篇 |
2015年 | 130篇 |
2014年 | 131篇 |
2013年 | 132篇 |
2012年 | 199篇 |
2011年 | 192篇 |
2010年 | 133篇 |
2009年 | 111篇 |
2008年 | 165篇 |
2007年 | 136篇 |
2006年 | 152篇 |
2005年 | 117篇 |
2004年 | 130篇 |
2003年 | 105篇 |
2002年 | 94篇 |
2001年 | 88篇 |
2000年 | 78篇 |
1999年 | 108篇 |
1998年 | 38篇 |
1997年 | 42篇 |
1996年 | 35篇 |
1995年 | 37篇 |
1994年 | 27篇 |
1993年 | 31篇 |
1992年 | 74篇 |
1991年 | 58篇 |
1990年 | 59篇 |
1989年 | 53篇 |
1988年 | 47篇 |
1987年 | 39篇 |
1986年 | 33篇 |
1985年 | 27篇 |
1984年 | 24篇 |
1983年 | 22篇 |
1982年 | 16篇 |
1981年 | 18篇 |
1980年 | 20篇 |
1979年 | 24篇 |
1978年 | 16篇 |
1977年 | 22篇 |
1975年 | 18篇 |
1974年 | 20篇 |
1973年 | 17篇 |
1972年 | 14篇 |
排序方式: 共有3383条查询结果,搜索用时 15 毫秒
901.
Role of glucagon-like peptide-1 in the pathogenesis and treatment of diabetes mellitus 总被引:6,自引:0,他引:6
De León DD Crutchlow MF Ham JY Stoffers DA 《The international journal of biochemistry & cell biology》2006,38(5-6):845-859
Glucagon-like peptide-1 (GLP-1) is an incretin hormone secreted from enteroendocrine L cells in response to ingested nutrients. The first recognized and most important action of GLP-1 is the potentiation of glucose-stimulated insulin secretion in beta-cells, mediated by activation of its seven transmembrane domain G-protein-coupled receptor. In addition to its insulinotropic actions, GLP-1 exerts islet-trophic effects by stimulating replication and differentiation and by decreasing apoptosis of beta-cells. The GLP-1 receptor is expressed in a variety of other tissues important for carbohydrate metabolism, including pancreatic alpha-cells, hypothalamus and brainstem, and proximal intestinal tract. GLP-1 also appears to exert important actions in liver, muscle and fat. Thus, GLP-1 suppresses glucagon secretion, promotes satiety, delays gastric emptying and stimulates peripheral glucose uptake. The impaired GLP-1 secretion observed in type 2 diabetes suggests that GLP-1 plays a role in the pathogenesis of this disorder. Thus, because of its multiple actions, GLP-1 is an attractive therapeutic target for the treatment of type 2 diabetes, and major interest has resulted in the development of a variety of GLP-1 receptor agonists for this purpose. Ongoing clinical trials have shown promising results and the first analogs of GLP-1 are expected to be available in the near future. 相似文献
902.
903.
Stabilization of poliovirus against heat inactivation 总被引:3,自引:0,他引:3
B L Dorval M Chow A M Klibanov 《Biochemical and biophysical research communications》1989,159(3):1177-1183
Fatty acids and related compounds, as well as many salts, stabilize poliovirus against heat inactivation. Addition of myristate to poliovirus prevents heat-induced conformational changes which are detected by trypsin degradation of the virion. Using equilibrium dialysis, we found that several molecules of myristate bind per virion. The relative stabilizing potencies of the salts can be explained by the Hofmeister effect. 相似文献
904.
Evanescent-wave microscopy: a new tool to gain insight into the control of transmitter release 总被引:2,自引:0,他引:2
Oheim M Loerke D Chow RH Stühmer W 《Philosophical transactions of the Royal Society of London. Series B, Biological sciences》1999,354(1381):307-318
Evanescent-wave excitation was used to visualize individual fluorescently labelled vesicles in an optical slice near the plasma membrane of bovine adrenal chromaffin cells. A standard upright microscope was modified to accommodate the optics used for directing a laser beam under a supracritical angle on to the glass-water interface on top of which the cells are grown. Whereas epi-illumination images appeared blurred and structureless, evanescent-wave excitation highlighted acridine orange-labelled vesicles as individual pinpoints. Three-dimensional (3D) trajectories of individual vesicles were obtained from time-resolved image stacks and used to characterize vesicles in terms of their average fluorescence F and mobility, expressed here as the 3D diffusion coefficient D(3). Based on the single-vesicle analysis, two groups of vesicles were identified. Transitions between these states were studied before and after stimulation of exocytosis by repetitive or maintained membrane depolarizations by elevated extracellular [K+]. Findings were interpreted as sequential transitions between the previously characterized pools of vesicles preceding the fusion step. The observed approach of vesicles to their docking sites was not explained in terms of free diffusion: most vesicles moved unidirectionally as if directed to their binding sites at the plasma membrane. Vesicle mobility at the membrane was low, such that the sites of docking and fusion were in close vicinity. Both the rim region and confined areas in the centre of the footprint region were the site of intense vesicle trafficking. 相似文献
905.
906.
Morgan G Smith S Pak J Marshak-Rothstein A Fissore R Osborne B 《Cell death and differentiation》1999,6(1):36-47
A mutant T-cell hybridoma line named mutant 51 was developed that, unlike the parental line, did not die after T-cell receptor (TCR) engagement and demonstrated reduced death in response to dexamethasone. Intracellular calcium measurements showed that available calcium stores were markedly reduced in the mutant cell line. Unlike control cells, secretion of IL-2 from mutant cells was also greatly reduced, although addition of exogenous IL-2 did not facilitate increased apoptosis. Although levels of the cell death gene product Nur77 were equivalent, additional studies showed that mutant cells expressed Nur77 predominantly in the cytoplasm following TCR engagement, while parental cells displayed a nuclear translocalization of Nur77. In addition, Fas levels and Fas ligand dependant killing were both markedly reduced in the mutant clone. From these data we hypothesize a role for available calcium stores and Nur77 nuclear localization in TCR-mediated apoptosis in T-cell hybridomas. 相似文献
907.
Annexin VI is a Ca(2+)-dependent membrane and phospholipid binding protein. It mediates a protein-protein interaction with the Ras p21 regulatory protein p120GAP. In this study we have mapped the binding site of GAP within the annexin VI protein. Using Far Western overlay binding assays and cell lysate competition studies we have mapped the site of interaction to the inter-lobe linker region; amino acids 325-363. Finally, using a GST fusion protein corresponding to this linker region we have demonstrated that cellular loading of the fusion protein into Rat-1 fibroblasts by electroporation blocks the interaction and co-immunoprecipitation of annexin VI and GAP. 相似文献
908.
When rabbit isolated gastric glands were stimulated via the cyclic AMP pathway, a phosphorylated protein band of about 120
kDa (pp120) was markedly increased in the apical membrane-rich fraction, concomitant with an increase in the amount of H,K-ATPase
and the phosphorylation of the cytoskeletal protein ezrin in the same fraction. The cytosolic fraction, but not other membrane
fractions, also contained a protein with common features to the membrane-bound pp120, i.e., comigration in two-dimensional
gels with a pI of ∼4.5, anomalous mobility in SDS-PAGE, reactivity to antibodies, and phosphorylation, indicating that these
two proteins were identical. The possibility that pp120 is vinculin was completely excluded. Using antibody against pp120,
this protein was found to be almost exclusively in the gastric parietal cell. Biochemical and immunohistochemical analyses
suggest that pp120 exists mainly in the cytosol, and that a small part of the protein binds to the apical membrane when the
parietal cell is stimulated via the cyclic AMP pathway. In the presence of histone, purified pp120 produced phosphorylation
on pp120 as well as histone. The inhibitor profile of this kinase activity is not consistent with any known kinase. We conclude
that pp120 is closely associated with a new type of kinase, and translocates from cytosol to the apical membrane when the
parietal cell is stimulated.
Received: 9 September 1998/Revised: 29 December 1998 相似文献
909.
910.
Ham C 《BMJ (Clinical research ed.)》1999,319(7223):1490-1492