全文获取类型
收费全文 | 9703篇 |
免费 | 792篇 |
国内免费 | 9篇 |
专业分类
10504篇 |
出版年
2023年 | 42篇 |
2022年 | 79篇 |
2021年 | 170篇 |
2020年 | 111篇 |
2019年 | 110篇 |
2018年 | 161篇 |
2017年 | 129篇 |
2016年 | 270篇 |
2015年 | 413篇 |
2014年 | 501篇 |
2013年 | 629篇 |
2012年 | 775篇 |
2011年 | 759篇 |
2010年 | 449篇 |
2009年 | 441篇 |
2008年 | 597篇 |
2007年 | 644篇 |
2006年 | 611篇 |
2005年 | 528篇 |
2004年 | 534篇 |
2003年 | 514篇 |
2002年 | 509篇 |
2001年 | 108篇 |
2000年 | 81篇 |
1999年 | 117篇 |
1998年 | 147篇 |
1997年 | 104篇 |
1996年 | 94篇 |
1995年 | 104篇 |
1994年 | 87篇 |
1993年 | 84篇 |
1992年 | 89篇 |
1991年 | 39篇 |
1990年 | 48篇 |
1989年 | 34篇 |
1988年 | 37篇 |
1987年 | 23篇 |
1986年 | 33篇 |
1985年 | 31篇 |
1984年 | 27篇 |
1983年 | 28篇 |
1982年 | 37篇 |
1981年 | 30篇 |
1980年 | 22篇 |
1979年 | 19篇 |
1978年 | 11篇 |
1977年 | 24篇 |
1976年 | 17篇 |
1974年 | 8篇 |
1973年 | 11篇 |
排序方式: 共有10000条查询结果,搜索用时 0 毫秒
21.
Marie Armani-Tourret Zhicheng Zhou Romain Gasser Isabelle Staropoli Vincent Cantaloube-Ferrieu Yann Benureau Javier Garcia-Perez Mayte Prez-Olmeda Valrie Lorin Bndicte Puissant-Lubrano Lambert Assoumou Constance Delaugerre Jean-Daniel Lelivre Yves Lvy Hugo Mouquet Guillaume Martin-Blondel Jose Alcami Fernando Arenzana-Seisdedos Jacques Izopet Philippe Colin Bernard Lagane 《PLoS pathogens》2021,17(4)
HIV-1 infects CD4 T lymphocytes (CD4TL) through binding the chemokine receptors CCR5 or CXCR4. CXCR4-using viruses are considered more pathogenic, linked to accelerated depletion of CD4TL and progression to AIDS. However, counterexamples to this paradigm are common, suggesting heterogeneity in the virulence of CXCR4-using viruses. Here, we investigated the role of the CXCR4 chemokine CXCL12 as a driving force behind virus virulence. In vitro, CXCL12 prevents HIV-1 from binding CXCR4 and entering CD4TL, but its role in HIV-1 transmission and propagation remains speculative. Through analysis of thirty envelope glycoproteins (Envs) from patients at different stages of infection, mostly treatment-naïve, we first interrogated whether sensitivity of viruses to inhibition by CXCL12 varies over time in infection. Results show that Envs resistant (RES) to CXCL12 are frequent in patients experiencing low CD4TL levels, most often late in infection, only rarely at the time of primary infection. Sensitivity assays to soluble CD4 or broadly neutralizing antibodies further showed that RES Envs adopt a more closed conformation with distinct antigenicity, compared to CXCL12-sensitive (SENS) Envs. At the level of the host cell, our results suggest that resistance is not due to improved fusion or binding to CD4, but owes to viruses using particular CXCR4 molecules weakly accessible to CXCL12. We finally asked whether the low CD4TL levels in patients are related to increased pathogenicity of RES viruses. Resistance actually provides viruses with an enhanced capacity to enter naive CD4TL when surrounded by CXCL12, which mirrors their situation in lymphoid organs, and to deplete bystander activated effector memory cells. Therefore, RES viruses seem more likely to deregulate CD4TL homeostasis. This work improves our understanding of the pathophysiology and the transmission of HIV-1 and suggests that RES viruses’ receptors could represent new therapeutic targets to help prevent CD4TL depletion in HIV+ patients on cART. 相似文献
22.
23.
For flexible peptides, nuclear Overhauser Effects (NOE) experiments do not provide enough information to ensure a correct definition of their solution structure. The use of distance constraints, derived from the knowledge of proton chemical shifts, is developed to restrict the number of possible conformations. In the case of flexible molecules, randomization appears as an important factor of the correct estimation of the chemical shifts from the 3D structure. The refinement of the solution structure of the highly flexible AVP-like parallel dimer is described to illustrate this process. 相似文献
24.
Analysis of macromolecular carbohydrates performed by gas liquid chromatography on Gregarina blaberae haemolymph showed the presence of hexoses (galactose, mannose, glucose), methyl-pentose (fucose), and hexosamines (N-acetylgalactosamine, N-acetylglucosamine). No trace of pentose or sialic acid or uronic acid was found. Mannose was the main neutral sugar. A change in the molar ratio of mannose consisting of an enrichment of female haemolymph occurred during larval-adult ecdysis. There was a parallel increase in glycoprotein staining with periodate-fuchsin after cellulose acetate electrophoresis of female haemolymph. 相似文献
25.
Bilateral electrolytic lesions restricted to the lateral, basolateral and basomedial amygdaloid nuclei in mice produced a lack of avoidance responses towards novel stimuli. While controls showed avoidance and burying reactions to a novel object introduced into their familiar environment, lesioned mice displayed a high number of approach responses and a low level of burying reactions. Furthermore, when given the opportunity to move around freely in simultaneously presented novel and familiar places, control mice at first exhibited avoidance reactions to the novel environment before showing novelty preference. There were no avoidance reactions in lesioned mice. These data are consistent with the hypothesis that amygdala plays a specific role in the regulation of defensive reactions. 相似文献
26.
27.
28.
Decapod crustaceans are relatively widespread in Jurassic deposits of Europe and a small number have been collected from the north-east of France. A new fossil of a macrurous decapod assigned to Eryma burgundiaca sp. nov., an erymid lobster, is described from this area and comparisons are made with closely allied species from Europe. Probable pagurid anomurous decapods are represented by Orhomalus magnificus sp. nov., Palaeopagurus acutus sp. nov. and Palaeopagurus neraudeaui sp. nov. No brachyurous decapods are presently known from the fauna. Based on the associated ammonites, the material is considered to be Callovian in age. 相似文献
29.
D J Drucker J Philippe L Jepeal J F Habener 《The Journal of biological chemistry》1987,262(32):15659-15665
30.