全文获取类型
收费全文 | 7880篇 |
免费 | 729篇 |
国内免费 | 2篇 |
出版年
2023年 | 33篇 |
2022年 | 54篇 |
2021年 | 182篇 |
2020年 | 117篇 |
2019年 | 136篇 |
2018年 | 170篇 |
2017年 | 177篇 |
2016年 | 220篇 |
2015年 | 417篇 |
2014年 | 466篇 |
2013年 | 591篇 |
2012年 | 729篇 |
2011年 | 697篇 |
2010年 | 439篇 |
2009年 | 408篇 |
2008年 | 564篇 |
2007年 | 505篇 |
2006年 | 495篇 |
2005年 | 437篇 |
2004年 | 464篇 |
2003年 | 329篇 |
2002年 | 372篇 |
2001年 | 80篇 |
2000年 | 43篇 |
1999年 | 71篇 |
1998年 | 88篇 |
1997年 | 53篇 |
1996年 | 31篇 |
1995年 | 26篇 |
1994年 | 25篇 |
1993年 | 31篇 |
1992年 | 14篇 |
1991年 | 15篇 |
1990年 | 20篇 |
1989年 | 14篇 |
1988年 | 7篇 |
1987年 | 10篇 |
1986年 | 6篇 |
1985年 | 5篇 |
1984年 | 12篇 |
1983年 | 7篇 |
1982年 | 8篇 |
1981年 | 7篇 |
1979年 | 3篇 |
1978年 | 4篇 |
1977年 | 2篇 |
1976年 | 3篇 |
1973年 | 3篇 |
1967年 | 2篇 |
1960年 | 3篇 |
排序方式: 共有8611条查询结果,搜索用时 15 毫秒
991.
Zelenak C Eberhard M Jilani K Qadri SM Macek B Lang F 《Cellular physiology and biochemistry》2012,29(1-2):171-180
Protein kinase CK1 (casein kinase 1) isoforms are involved in the regulation of various physiological functions including apoptosis. The specific CK1 inhibitor D4476 may either inhibit or foster apoptosis. Similar to apoptosis of nucleated cells, eryptosis, the suicidal death of erythrocytes, is paralleled by cell shrinkage and cell membrane scrambling with phosphatidylserine exposure at the cell surface. Triggers of eryptosis include increase of cytosolic Ca(2+) activity following energy depletion (removal of glucose) or oxidative stress (exposure to the oxidant tert-butyl hydroperoxide [TBOOH]). Western blotting was utilized to verify that erythrocytes express the protein kinase CK1α, and FACS analysis to determine whether the CK1 inhibitor D4476 and CK1α activator pyrvinium pamoate modify forward scatter (reflecting cell volume), annexin V binding (reflecting phosphatidylserine exposure), and Fluo3 fluorescence (reflecting cytosolic Ca(2+) activity). As a result, both, human and murine erythrocytes express CK1 isoform α. Glucose depletion (48 hours) and exposure to 0.3 mM TBOOH (30 minutes) both decreased forward scatter, increased annexin V binding and increased Fluo3 fluorescence. CK1 inhibitor D4476 (10 μM) significantly blunted the decrease in forward scatter, the increase in annexin V binding and the increase in Fluo 3 fluorescence. (R)-DRF053, another CK1 inhibitor, similarly blunted the increase in annexin V binding upon glucose depletion. The CK1α specific activator pyrvinium pamoate (10 μM) significantly enhanced the increase in annexin V binding and Fluo3 fluorescence upon glucose depletion and TBOOH exposure. In the presence of glucose, pyrvinium pamoate slightly but significantly increased Fluo3 fluorescence. In conclusion, CK1 isoform α participates in the regulation of erythrocyte programmed cell death by modulating cytosolic Ca(2+) activity. 相似文献
992.
993.
Totzeck M Hendgen-Cotta UB Rammos C Petrescu AM Meyer C Balzer J Kelm M Rassaf T 《Nitric oxide》2012,26(4):211-216
Myoglobin is presumably the most studied protein in biology. Its functional properties as a dioxygen storage and facilitator of dioxygen transport are widely acknowledged. Experimental evidence also implicates an essential role for myoglobin in the heart in regulating nitric oxide homeostasis. Under normoxia, oxygenated myoglobin can scavenge excessive nitric oxide, while under hypoxia, deoxygenated myoglobin can reduce nitrite, an oxidative product of nitric oxide, to bioactive nitric oxide. Myoglobin-driven nitrite reduction can protect the heart from ischemia and reperfusion injury. While horse and mouse myoglobin have been previously described to reduce nitrite under these conditions, a comparable activity has not been detected in human myoglobin. We here show that human myoglobin is a fully functional nitrite reductase. To study the role of human myoglobin for nitric oxide homeostasis we used repeated photometric wavelength scans and chemiluminescence based experiments. The results revealed that oxygenated human myoglobin reacts with nitrite-derived nitric oxide to form ferric myoglobin and that deoxygenated human myoglobin acts as a nitrite reductase in vitro and in situ. Rates of both nitric oxide scavenging and nitrite reduction were significantly higher in human compared to horse myoglobin. These data extend the existing knowledge about the functional properties of human myoglobin and are the basis for further translational studies towards the importance of myoglobin for nitric oxide metabolism in humans. 相似文献
994.
In long-range transport of cargo, prototypical kinesin-1 steps along a single protofilament on the microtubule, an astonishing behavior given the number of theoretically available binding sites on adjacent protofilaments. Using a laser trap assay, we analyzed the trajectories of several representatives from the kinesin-2 class on freely suspended microtubules. In stark contrast to kinesin-1, these motors display a wide range of left-handed spiraling around microtubules and thus generate torque during cargo transport. We provide direct evidence that kinesin's neck region determines the torque-generating properties. A model system based on kinesin-1 corroborates this result: disrupting the stability of the neck by inserting flexible peptide stretches resulted in pronounced left-handed spiraling. Mimicking neck stability by crosslinking significantly reduced the spiraling of the motor up to the point of protofilament tracking. Finally, we present a model that explains the physical basis of kinesin's spiraling around the microtubule. 相似文献
995.
996.
Henoch S. Hong Fareed Ahmad Johanna M. Eberhard Nupur Bhatnagar Benjamin A. Bollmann Phillip Keudel Matthias Ballmaier Margot Zielinska-Skowronek Reinhold E. Schmidt Dirk Meyer-Olson 《PloS one》2012,7(9)
NK cells are pivotal sentinels of the innate immune system and distinct subpopulations in peripheral blood have been described. A number of studies addressed HIV-induced alterations of NK cell phenotype and functionality mainly focusing on CD56dimCD16+ and CD56−CD16+ NK cells. However, the impact of HIV-infection on CD56bright NK cells is less well understood. Here we report a rise of CD56bright NK cells in HIV-infected individuals, which lack CCR7-expression and strongly correlate with HIV viral load. CCR7−CD56bright NK cells were characterized by increased cytolytic potential, higher activation states and a more differentiated phenotype. These cells thus acquired a number of features of CD56dimCD16+ NK cells. Furthermore, CD56bright NK cells from HIV patients exhibited higher degranulation levels compared to uninfected individuals. Thus, chronic HIV-infection is associated with a phenotypic and functional shift of CD56bright NK cells, which provides a novel aspect of HIV-associated pathogenesis within the NK cell compartment. 相似文献
997.
Claudia M. Casanova Peter Sehr Kerstin Putzker Matthias W. Hentze Beate Neumann Kent E. Duncan Christian Thoma 《PloS one》2012,7(9)
Proteins that promote angiogenesis, such as vascular endothelial growth factor (VEGF), are major targets for cancer therapy. Accordingly, proteins that specifically activate expression of factors like VEGF are potential alternative therapeutic targets and may help to combat evasive resistance to angiogenesis inhibitors. VEGF mRNA contains two internal ribosome entry sites (IRESs) that enable selective activation of VEGF protein synthesis under hypoxic conditions that trigger angiogenesis. To identify novel regulators of VEGF IRES-driven translation in human cells, we have developed a high-throughput screening approach that combines siRNA treatment with transfection of a VEGF-IRES reporter mRNA. We identified the kinase MAPK3 as a novel positive regulator of VEGF IRES-driven translation and have validated its regulatory effect on endogenous VEGF. Our automated method is scalable and readily adapted for use with other mRNA regulatory elements. Consequently, it should be a generally useful approach for high-throughput identification of novel regulators of mRNA translation. 相似文献
998.
999.
1000.