全文获取类型
收费全文 | 51932篇 |
免费 | 4182篇 |
国内免费 | 4131篇 |
出版年
2024年 | 126篇 |
2023年 | 655篇 |
2022年 | 1625篇 |
2021年 | 2762篇 |
2020年 | 1767篇 |
2019年 | 2165篇 |
2018年 | 2131篇 |
2017年 | 1571篇 |
2016年 | 2104篇 |
2015年 | 3121篇 |
2014年 | 3674篇 |
2013年 | 3948篇 |
2012年 | 4730篇 |
2011年 | 4258篇 |
2010年 | 2657篇 |
2009年 | 2341篇 |
2008年 | 2670篇 |
2007年 | 2403篇 |
2006年 | 2148篇 |
2005年 | 1873篇 |
2004年 | 1562篇 |
2003年 | 1328篇 |
2002年 | 1204篇 |
2001年 | 989篇 |
2000年 | 838篇 |
1999年 | 805篇 |
1998年 | 540篇 |
1997年 | 468篇 |
1996年 | 489篇 |
1995年 | 388篇 |
1994年 | 416篇 |
1993年 | 295篇 |
1992年 | 368篇 |
1991年 | 296篇 |
1990年 | 235篇 |
1989年 | 229篇 |
1988年 | 179篇 |
1987年 | 167篇 |
1986年 | 141篇 |
1985年 | 106篇 |
1984年 | 115篇 |
1983年 | 77篇 |
1982年 | 53篇 |
1981年 | 30篇 |
1980年 | 23篇 |
1979年 | 30篇 |
1977年 | 16篇 |
1976年 | 15篇 |
1974年 | 12篇 |
1973年 | 12篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
1.
2.
Nonstructural protein 5A (NS5A) of hepatitis C virus (HCV) is an indispensable component of the HCV replication and assembly machineries. Although its precise mechanism of action is not yet clear, current evidence indicates that its structure and function are regulated by the cellular peptidylprolyl isomerase cyclophilin A (CyPA). CyPA binds to proline residues in the C-terminal half of NS5A, in a distributed fashion, and modulates the structure of the disordered domains II and III. Cyclophilin inhibitors (CPIs), including cyclosporine (CsA) and its nonimmunosuppressive derivatives, inhibit HCV infection of diverse genotypes, both in vitro and in vivo. Here we report a mechanism by which CPIs inhibit HCV infection and demonstrate that CPIs can suppress HCV assembly in addition to their well-documented inhibitory effect on RNA replication. Although the interaction between NS5A and other viral proteins is not affected by CPIs, RNA binding by NS5A in cell culture-based HCV (HCVcc)-infected cells is significantly inhibited by CPI treatment, and sensitivity of RNA binding is correlated with previously characterized CyPA dependence or CsA sensitivity of HCV mutants. Furthermore, the difference in CyPA dependence between a subgenomic and a full-length replicon of JFH-1 was due, at least in part, to an additional role that CyPA plays in HCV assembly, a conclusion that is supported by experiments with the clinical CPI alisporivir. The host-directed nature and the ability to interfere with more than one step in the HCV life cycle may result in a higher genetic barrier to resistance for this class of HCV inhibitors. 相似文献
3.
The functioning of the vertebrate eye depends on its absolute size, which is presumably adapted to specific needs. Eye size variation in lidless and spectacled colubrid snakes was investigated, including 839 specimens belonging to 49 genera, 66 species and subspecies. Variations of adult eye diameters (EDs) in both absolute and relative terms between species were correlated with parameters reflecting behavioral ecology. In absolute terms, eye of arboreal species was larger than in terrestrial and semiaquatic species. For diurnal species, EDs of terrestrial species do not differ from semiaquatic species; for nocturnal species the ED of terrestrial species is larger than fossorial species but not different from semiaquatic species. In relative terms, ED did not differ significantly by habitat for diurnal species. Although the ED of terrestrial species is larger than fossorial species there were no differences for nocturnal species between semiaquatic and fossorial snakes. In contrast to other vertebrates studied to date, colubrid EDs in absolute and relative terms are larger in diurnal than in nocturnal species. These observations suggest that among colubrid snakes, eye size variation reflects adaptation to specific habitats, foraging strategies and daily activities, independently of phylogeny. J. Morphol. 2012. © 2012 Wiley Periodicals, Inc. 相似文献
4.
Tao Tian Danhua Yao Lei Zheng Zhiyuan Zhou Yantao Duan Bin Liu Pengfei Wang Yousheng Li 《Cell death & disease》2020,11(12)
Previously, we confirmed that sphingosine kinase 1 (SphK1) inhibition improves sepsis-associated liver injury. High-mobility group box 1 (HMGB1) translocation participates in the development of acute liver failure. However, little information is available on the association between SphK1 and HMGB1 translocation during sepsis-associated liver injury. In the present study, we aimed to explore the effect of SphK1 inhibition on HMGB1 translocation and the underlying mechanism during sepsis-associated liver injury. Primary Kupffer cells and hepatocytes were isolated from SD rats. The rat model of sepsis-associated liver damage was induced by intraperitoneal injection with lipopolysaccharide (LPS). We confirmed that Kupffer cells were the cells primarily secreting HMGB1 in the liver after LPS stimulation. LPS-mediated HMGB1 expression, intracellular translocation, and acetylation were dramatically decreased by SphK1 inhibition. Nuclear histone deacetyltransferase 4 (HDAC4) translocation and E1A-associated protein p300 (p300) expression regulating the acetylation of HMGB1 were also suppressed by SphK1 inhibition. HDAC4 intracellular translocation has been reported to be controlled by the phosphorylation of HDAC4. The phosphorylation of HDAC4 is modulated by CaMKII-δ. However, these changes were completely blocked by SphK1 inhibition. Additionally, by performing coimmunoprecipitation and pull-down assays, we revealed that SphK1 can directly interact with CaMKII-δ. The colocalization of SphK1 and CaMKII-δ was verified in human liver tissues with sepsis-associated liver injury. In conclusion, SphK1 inhibition diminishes HMGB1 intracellular translocation in sepsis-associated liver injury. The mechanism is associated with the direct interaction of SphK1 and CaMKII-δ.Subject terms: Hepatotoxicity, Sepsis 相似文献
5.
6.
7.
Plant and Soil - To investigate the effects of polystyrene microplastics (PS-beads) on the soil properties, photosynthesis of Flowering Chinese cabbage, the rhizosphere microbial community and... 相似文献
8.
Yunfan Sun Liang Wu Yu Zhong Kaiqian Zhou Yong Hou Zifei Wang Zefan Zhang Jiarui Xie Chunqing Wang Dandan Chen Yaling Huang Xiaochan Wei Yinghong Shi Zhikun Zhao Yuehua Li Ziwei Guo Qichao Yu Liqin Xu Jia Fan 《Cell》2021,184(2):404-421.e16
- Download : Download high-res image (233KB)
- Download : Download full-size image
9.
1. As for some other spring‐feeding moths, adult flight of Epirrita autumnata (Lepidoptera: Geometridae) occurs in late autumn. Late‐season flight is a result of a prolonged pupal period. Potential evolutionary explanations for this phenological pattern are evaluated. 2. In a laboratory rearing, there was a weak correlation between pupation date and the time of adult emergence. A substantial genetic difference in pupal period was found between two geographic populations. Adaptive evolution of eclosion time can thus be expected. 3. Metabolic costs of a prolonged pupal period were found to be moderate but still of some ecological significance. Pupal mortality is likely to form the main cost of the prolonged pupal period. 4. Mortality rates of adults, exposed in the field, showed a declining temporal trend from late summer to normal eclosion time in autumn. Lower predation pressure on adults may constitute the decisive selective advantage of late‐season flight. It is suggested that ants, not birds, were the main predators responsible for the temporal trend. 5. Egg mortality was estimated to be low; it is thus unlikely that the late adult period is selected for to reduce the time during which eggs are exposed to predators. 6. In a laboratory experiment, oviposition success was maximal at the time of actual flight peak of E. autumnata, however penalties resulting from sub‐optimal timing of oviposition remained limited. 相似文献