全文获取类型
收费全文 | 2102篇 |
免费 | 213篇 |
国内免费 | 2篇 |
专业分类
2317篇 |
出版年
2023年 | 14篇 |
2022年 | 30篇 |
2021年 | 32篇 |
2020年 | 22篇 |
2019年 | 21篇 |
2018年 | 23篇 |
2017年 | 22篇 |
2016年 | 43篇 |
2015年 | 98篇 |
2014年 | 110篇 |
2013年 | 129篇 |
2012年 | 154篇 |
2011年 | 158篇 |
2010年 | 99篇 |
2009年 | 79篇 |
2008年 | 103篇 |
2007年 | 88篇 |
2006年 | 125篇 |
2005年 | 92篇 |
2004年 | 88篇 |
2003年 | 74篇 |
2002年 | 72篇 |
2001年 | 61篇 |
2000年 | 67篇 |
1999年 | 55篇 |
1998年 | 17篇 |
1997年 | 20篇 |
1996年 | 13篇 |
1995年 | 13篇 |
1994年 | 14篇 |
1993年 | 12篇 |
1992年 | 24篇 |
1991年 | 32篇 |
1990年 | 13篇 |
1989年 | 23篇 |
1988年 | 26篇 |
1987年 | 19篇 |
1986年 | 31篇 |
1985年 | 26篇 |
1984年 | 19篇 |
1983年 | 16篇 |
1982年 | 8篇 |
1980年 | 10篇 |
1979年 | 10篇 |
1978年 | 15篇 |
1976年 | 14篇 |
1975年 | 15篇 |
1973年 | 9篇 |
1969年 | 6篇 |
1966年 | 6篇 |
排序方式: 共有2317条查询结果,搜索用时 15 毫秒
11.
A single immunization of Lewis rats with purified acetylcholine receptor (AChR) emulsified in adjuvant typically stimulates the production of oligoclonal AChR-reactive antibodies (as demonstrated by IEF) dominated by the IgG2a subclass, of moderate but clonotypically heterogeneous relative Ag-binding avidity, and capable of inducing symptoms of experimental autoimmune myasthenia gravis. Although similar immunization of Wistar Furth rats produces AChR-reactive antibodies with similar characteristics of clonotypic heterogeneity, avidity, and isotype expression, no detectable signs of AChR-dependent muscle impairment is observed. This contrasts the ability to induce impaired AChR function upon the passive transfer of pre-formed Lewis anti-AChR antibodies into naive Wistar Furth rats, suggesting that disease resistance in this model is not conferred at the level of the AChR itself. Moreover, if more aggressive immunization protocols are used (i.e., multiple injections of AChR), a transient breakthrough of AChR-dependent muscle dysfunction can be induced directly in the Wistar Furth strain indicating that the potential for the production of disease-causing antibodies does exist in the Wistar Furth repertoire. IEF analysis of Wistar Furth anti-AChR antibodies has revealed that hyperimmunization results in modified antibody clonotype expression that might explain changing expression of disease symptoms; however, explanations for the apparent "resistance" of Wistar Furth rats to disease induction are likely to be complex. 相似文献
12.
13.
Protective effects of soluble CR1 in complement- and neutrophil-mediated tissue injury. 总被引:7,自引:0,他引:7
M S Mulligan C G Yeh A R Rudolph P A Ward 《Journal of immunology (Baltimore, Md. : 1950)》1992,148(5):1479-1485
Complement activation is an important step for triggering of acute inflammatory reactions. Soluble human recombinant complement receptor type 1 (sCR1) blocks complement activation by both classical and alternative pathways. In addition to glycogen-induced peritonitis, three models of complement-dependent acute inflammatory injury have been used to assess the protective effects of sCR1: lung and dermal injury after intraalveolar or intradermal deposition of IgG immune complexes; acute lung injury resulting from intravascular activation of complement after the i.v. injection of cobra venom factor; and acute skin and lung injury (at 4 h) after thermal trauma involving 25 to 30% total body surface area. Vascular injury was quantified by increases in vascular permeability, hemorrhage, neutrophil infiltration, and, as indicated, tissue water content. Intravenous infusion of sCR1 reduced lung and dermal vascular injury in all models studied. In glycogen-induced peritoneal exudates sCR1-reduced neutrophil accumulation by 79%. In animals undergoing IgG immune complex-induced alveolitis, sCR1 treatment reduced vascular permeability and hemorrhage by 72 and 71%, respectively, and tissue accumulation of neutrophils was reduced by 68%. After cobra venom factor injection, sCR1 reduced increases in lung vascular permeability by 67%, hemorrhage by 73%, and lung myeloperoxidase content by 55%. Four hours after thermal injury of skin, sCR1-treated animals demonstrated significant protection against lung injury; increases in vascular permeability and hemorrhage were reduced by 45 and 46%, respectively, and myeloperoxidase content was lowered by 39%. In thermal injury of the skin, sCR1 injection reduced dermal vascular permeability by 25% at 1 h (p = NS) and 44% at 4 h. Water content in skin biopsies was also decreased. There was a dose-response relationship between the amount of sCR1 infused and the extent of protection in each of the injury models. These data demonstrate that sCR1 offers significant protection against complement-dependent tissue injury in the animal models studied and that the protective effects are related to reduced neutrophil content. 相似文献
14.
Interactions of aminopyridines with potassium channels of squid axon membranes. 总被引:26,自引:0,他引:26 下载免费PDF全文
The effects of aminopyridines on ionic conductances of the squid giant axon membrane were examined using voltage clamp and internal perfusion techniques. 4-Aminopyridine (4-AP) reduced potassium currents, but had no effect upon transient sodium currents. The block of potassium channels by 4-AP was substantially less with (a) strong depolarization to positive membrane potentials, (b) increasing the duration of a given depolarizing step, and (c) increasing the frequency of step depolarizations. Experiments with high external potassium concentrations revealed that the effect of 4-AP was independent of the direction of potassium ion movement. Both 3- and 2-aminopyridine were indistinguishable from 4-AP except in potency. It is concluded that aminopyrimidines may be used as tools to block the potassium conductance in excitable membranes, but only within certain specific voltage and frequency limits. 相似文献
15.
Rylie B. Walsh Erica C. Dresselhaus Agata N. Becalska Matthew J. Zunitch Cassandra R. Blanchette Amy L. Scalera Tania Lemos So Min Lee Julia Apiki ShiYu Wang Berith Isaac Anna Yeh Kate Koles Avital A. Rodal 《The Journal of cell biology》2021,220(8)
Neuronal extracellular vesicles (EVs) play important roles in intercellular communication and pathogenic protein propagation in neurological disease. However, it remains unclear how cargoes are selectively packaged into neuronal EVs. Here, we show that loss of the endosomal retromer complex leads to accumulation of EV cargoes including amyloid precursor protein (APP), synaptotagmin-4 (Syt4), and neuroglian (Nrg) at Drosophila motor neuron presynaptic terminals, resulting in increased release of these cargoes in EVs. By systematically exploring known retromer-dependent trafficking mechanisms, we show that EV regulation is separable from several previously identified roles of neuronal retromer. Conversely, mutations in rab11 and rab4, regulators of endosome-plasma membrane recycling, cause reduced EV cargo levels, and rab11 suppresses cargo accumulation in retromer mutants. Thus, EV traffic reflects a balance between Rab4/Rab11 recycling and retromer-dependent removal from EV precursor compartments. Our data shed light on previous studies implicating Rab11 and retromer in competing pathways in Alzheimer’s disease, and suggest that misregulated EV traffic may be an underlying defect. 相似文献
16.
17.
18.
19.
Wei-Lan Yeh Keiko Shioda Kathryn R. Coser Danielle Rivizzigno Kristen R. McSweeney Toshi Shioda 《PloS one》2013,8(4)
Fulvestrant is a representative pure antiestrogen and a Selective Estrogen Receptor Down-regulator (SERD). In contrast to the Selective Estrogen Receptor Modulators (SERMs) such as 4-hydroxytamoxifen that bind to estrogen receptor α (ERα) as antagonists or partial agonists, fulvestrant causes proteasomal degradation of ERα protein, shutting down the estrogen signaling to induce proliferation arrest and apoptosis of estrogen-dependent breast cancer cells. We performed genome-wide RNAi knockdown screenings for protein kinases required for fulvestrant-induced apoptosis of the MCF-7 estrogen-dependent human breast caner cells and identified the c-Src tyrosine kinase (CSK), a negative regulator of the oncoprotein c-Src and related protein tyrosine kinases, as one of the necessary molecules. Whereas RNAi knockdown of CSK in MCF-7 cells by shRNA-expressing lentiviruses strongly suppressed fulvestrant-induced cell death, CSK knockdown did not affect cytocidal actions of 4-hydroxytamoxifen or paclitaxel, a chemotherapeutic agent. In the absence of CSK, fulvestrant-induced proteasomal degradation of ERα protein was suppressed in both MCF-7 and T47D estrogen-dependent breast cancer cells whereas the TP53-mutated T47D cells were resistant to the cytocidal action of fulvestrant in the presence or absence of CSK. MCF-7 cell sensitivities to fulvestrant-induced cell death or ERα protein degradation was not affected by small-molecular-weight inhibitors of the tyrosine kinase activity of c-Src, suggesting possible involvement of other signaling molecules in CSK-dependent MCF-7 cell death induced by fulvestrant. Our observations suggest the importance of CSK in the determination of cellular sensitivity to the cytocidal action of fulvestrant. 相似文献
20.
Chun-Ho Yun Hiram G. Bezerra Tung-Hsin Wu Fei-Shih Yang Chuan-Chuan Liu Yih-Jer Wu Jen-Yuan Kuo Chung-Lieh Hung Jason Jeun-Shenn Lee Charles Jia-Yin Hou Hung-I Yeh Chris T. Longenecker Ricardo C. Cury 《PloS one》2013,8(4)