全文获取类型
收费全文 | 23374篇 |
免费 | 1857篇 |
国内免费 | 1942篇 |
出版年
2024年 | 37篇 |
2023年 | 256篇 |
2022年 | 646篇 |
2021年 | 1261篇 |
2020年 | 860篇 |
2019年 | 1017篇 |
2018年 | 972篇 |
2017年 | 698篇 |
2016年 | 1011篇 |
2015年 | 1464篇 |
2014年 | 1763篇 |
2013年 | 1831篇 |
2012年 | 2140篇 |
2011年 | 1893篇 |
2010年 | 1161篇 |
2009年 | 1041篇 |
2008年 | 1181篇 |
2007年 | 1036篇 |
2006年 | 903篇 |
2005年 | 817篇 |
2004年 | 670篇 |
2003年 | 608篇 |
2002年 | 497篇 |
2001年 | 404篇 |
2000年 | 378篇 |
1999年 | 381篇 |
1998年 | 243篇 |
1997年 | 218篇 |
1996年 | 225篇 |
1995年 | 193篇 |
1994年 | 214篇 |
1993年 | 155篇 |
1992年 | 181篇 |
1991年 | 155篇 |
1990年 | 113篇 |
1989年 | 101篇 |
1988年 | 75篇 |
1987年 | 71篇 |
1986年 | 52篇 |
1985年 | 51篇 |
1984年 | 49篇 |
1983年 | 29篇 |
1982年 | 24篇 |
1981年 | 16篇 |
1980年 | 7篇 |
1979年 | 20篇 |
1978年 | 8篇 |
1976年 | 7篇 |
1975年 | 5篇 |
1972年 | 5篇 |
排序方式: 共有10000条查询结果,搜索用时 46 毫秒
1.
2.
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
3.
4.
5.
6.
Plant and Soil - Seeds are involved in the transmission of microorganisms from one plant generation to the next, acting as initial inoculum for the plant microbiome, therefore provide a key source... 相似文献
7.
Peng Wang Ronghua Luo Min Zhang Yaqing Wang Tianzhang Song Tingting Tao Zhongyu Li Lin Jin Hongyi Zheng Wenwen Chen Mengqian Zhao Yongtang Zheng Jianhua Qin 《Cell death & disease》2020,11(12)
COVID-19, caused by SARS-CoV-2, is an acute and rapidly developing pandemic, which leads to a global health crisis. SARS-CoV-2 primarily attacks human alveoli and causes severe lung infection and damage. To better understand the molecular basis of this disease, we sought to characterize the responses of alveolar epithelium and its adjacent microvascular endothelium to viral infection under a co-culture system. SARS-CoV-2 infection caused massive virus replication and dramatic organelles remodeling in alveolar epithelial cells, alone. While, viral infection affected endothelial cells in an indirect manner, which was mediated by infected alveolar epithelium. Proteomics analysis and TEM examinations showed viral infection caused global proteomic modulations and marked ultrastructural changes in both epithelial cells and endothelial cells under the co-culture system. In particular, viral infection elicited global protein changes and structural reorganizations across many sub-cellular compartments in epithelial cells. Among the affected organelles, mitochondrion seems to be a primary target organelle. Besides, according to EM and proteomic results, we identified Daurisoline, a potent autophagy inhibitor, could inhibit virus replication effectively in host cells. Collectively, our study revealed an unrecognized cross-talk between epithelium and endothelium, which contributed to alveolar–capillary injury during SARS-CoV-2 infection. These new findings will expand our understanding of COVID-19 and may also be helpful for targeted drug development.Subject terms: Mechanisms of disease, Viral infection 相似文献
8.
Peng Chen Pranjal Swarup Wojciech Michal Matkowski Adams Wai Kin Kong Su Han Zhihe Zhang Hou Rong 《Ecology and evolution》2020,10(7):3561-3573
- As a highly endangered species, the giant panda (panda) has attracted significant attention in the past decades. Considerable efforts have been put on panda conservation and reproduction, offering the promising outcome of maintaining the population size of pandas. To evaluate the effectiveness of conservation and management strategies, recognizing individual pandas is critical. However, it remains a challenging task because the existing methods, such as traditional tracking method, discrimination method based on footprint identification, and molecular biology method, are invasive, inaccurate, expensive, or challenging to perform. The advances of imaging technologies have led to the wide applications of digital images and videos in panda conservation and management, which makes it possible for individual panda recognition in a noninvasive manner by using image‐based panda face recognition method.
- In recent years, deep learning has achieved great success in the field of computer vision and pattern recognition. For panda face recognition, a fully automatic deep learning algorithm which consists of a sequence of deep neural networks (DNNs) used for panda face detection, segmentation, alignment, and identity prediction is developed in this study. To develop and evaluate the algorithm, the largest panda image dataset containing 6,441 images from 218 different pandas, which is 39.78% of captive pandas in the world, is established.
- The algorithm achieved 96.27% accuracy in panda recognition and 100% accuracy in detection.
- This study shows that panda faces can be used for panda recognition. It enables the use of the cameras installed in their habitat for monitoring their population and behavior. This noninvasive approach is much more cost‐effective than the approaches used in the previous panda surveys.
9.
Molecular dynamics (MD) simulations of phosphatidylinositol (4,5)-bisphosphate (PIP2) and phosphatidylinositol (3,4,5)-trisphosphate (PIP3) in 1-palmitoyl 2-oleoyl phosphatidylcholine (POPC) bilayers indicate that the inositol rings are tilted ∼40° with respect to the bilayer surface, as compared with 17° for the P-N vector of POPC. Multiple minima were obtained for the ring twist (analogous to roll for an airplane). The phosphates at position 1 of PIP2 and PIP3 are within an Ångström of the plane formed by the phosphates of POPC; lipids in the surrounding shell are depressed by 0.5-0.8 Å, but otherwise the phosphoinositides do not substantially perturb the bilayer. Finite size artifacts for ion distributions are apparent for systems of ∼26 waters/lipid, but, based on simulations with a fourfold increase of the aqueous phase, the phosphoinositide positions and orientations do not show significant size effects. Electrostatic potentials evaluated from Poisson-Boltzmann (PB) calculations show a strong dependence of potential height and ring orientation, with the maxima on the −25 mV surfaces (17.1 ± 0.1 Å for PIP2 and 19.4 ± 0.3 Å for PIP3) occurring near the most populated orientations from MD. These surfaces are well above the background height of 10 Å estimated for negatively charged cell membranes, as would be expected for lipids involved in cellular signaling. PB calculations on microscopically flat bilayers yield similar maxima as the MD-based (microscopically rough) systems, but show less fine structure and do not clearly indicate the most probable regions. Electrostatic free energies of interaction with pentalysine are also similar for the rough and flat systems. These results support the utility of a rigid/flat bilayer model for PB-based studies of PIP2 and PIP3 as long as the orientations are judiciously chosen. 相似文献
10.