全文获取类型
收费全文 | 1185篇 |
免费 | 127篇 |
国内免费 | 1篇 |
出版年
2023年 | 13篇 |
2022年 | 36篇 |
2021年 | 66篇 |
2020年 | 27篇 |
2019年 | 29篇 |
2018年 | 38篇 |
2017年 | 34篇 |
2016年 | 59篇 |
2015年 | 103篇 |
2014年 | 88篇 |
2013年 | 104篇 |
2012年 | 125篇 |
2011年 | 109篇 |
2010年 | 48篇 |
2009年 | 37篇 |
2008年 | 37篇 |
2007年 | 59篇 |
2006年 | 52篇 |
2005年 | 33篇 |
2004年 | 36篇 |
2003年 | 23篇 |
2002年 | 23篇 |
2001年 | 10篇 |
2000年 | 8篇 |
1999年 | 8篇 |
1998年 | 2篇 |
1997年 | 4篇 |
1996年 | 3篇 |
1995年 | 5篇 |
1994年 | 3篇 |
1993年 | 5篇 |
1992年 | 6篇 |
1991年 | 3篇 |
1990年 | 3篇 |
1989年 | 2篇 |
1987年 | 3篇 |
1986年 | 5篇 |
1985年 | 5篇 |
1984年 | 8篇 |
1983年 | 6篇 |
1982年 | 5篇 |
1981年 | 3篇 |
1980年 | 3篇 |
1977年 | 4篇 |
1976年 | 3篇 |
1974年 | 3篇 |
1968年 | 2篇 |
1967年 | 2篇 |
1965年 | 2篇 |
1931年 | 2篇 |
排序方式: 共有1313条查询结果,搜索用时 15 毫秒
101.
102.
Space exploration by dendritic cells requires maintenance of myosin II activity by IP3 receptor 1
下载免费PDF全文
![点击此处可从《The EMBO journal》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Paola Solanes Marine Bretou Franziska Lautenschlaeger Paolo Maiuri Emmanuel Terriac Maria‐Isabel Thoulouze Pierre Launay Matthieu Piel Pablo Vargas Ana‐Maria Lennon‐Duménil 《The EMBO journal》2015,34(6):798-810
Dendritic cells (DCs) patrol the interstitial space of peripheral tissues. The mechanisms that regulate their migration in such constrained environment remain unknown. We here investigated the role of calcium in immature DCs migrating in confinement. We found that they displayed calcium oscillations that were independent of extracellular calcium and more frequently observed in DCs undergoing strong speed fluctuations. In these cells, calcium spikes were associated with fast motility phases. IP3 receptors (IP3Rs) channels, which allow calcium release from the endoplasmic reticulum, were identified as required for immature DCs to migrate at fast speed. The IP3R1 isoform was further shown to specifically regulate the locomotion persistence of immature DCs, that is, their capacity to maintain directional migration. This function of IP3R1 results from its ability to control the phosphorylation levels of myosin II regulatory light chain (MLC) and the back/front polarization of the motor protein. We propose that by upholding myosin II activity, constitutive calcium release from the ER through IP3R1 maintains DC polarity during migration in confinement, facilitating the exploration of their environment. 相似文献
103.
104.
105.
Chii?J. Chan Andrew?E. Ekpenyong Stefan Golfier Wenhong Li Kevin?J. Chalut Oliver Otto Jens Elgeti Jochen Guck Franziska Lautenschl?ger 《Biophysical journal》2015,108(8):1856-1869
The cellular cytoskeleton is crucial for many cellular functions such as cell motility and wound healing, as well as other processes that require shape change or force generation. Actin is one cytoskeleton component that regulates cell mechanics. Important properties driving this regulation include the amount of actin, its level of cross-linking, and its coordination with the activity of specific molecular motors like myosin. While studies investigating the contribution of myosin activity to cell mechanics have been performed on cells attached to a substrate, we investigated mechanical properties of cells in suspension. To do this, we used multiple probes for cell mechanics including a microfluidic optical stretcher, a microfluidic microcirculation mimetic, and real-time deformability cytometry. We found that nonadherent blood cells, cells arrested in mitosis, and naturally adherent cells brought into suspension, stiffen and become more solidlike upon myosin inhibition across multiple timescales (milliseconds to minutes). Our results hold across several pharmacological and genetic perturbations targeting myosin. Our findings suggest that myosin II activity contributes to increased whole-cell compliance and fluidity. This finding is contrary to what has been reported for cells attached to a substrate, which stiffen via active myosin driven prestress. Our results establish the importance of myosin II as an active component in modulating suspended cell mechanics, with a functional role distinctly different from that for substrate-adhered cells. 相似文献
106.
The plasma membrane is a highly complex, organized structure where the lateral organization of signaling proteins is tightly regulated. In the case of Ras proteins, it has been suggested that the differential activity of the various isoforms is due to protein localization in separate membrane compartments. To date, direct visualization of such compartmentalization has been achieved only by electron microscopy on membrane sheets. Here, we combine photoactivated light microscopy with quantitative statistical analysis to visualize protein distribution in intact cells. In particular, we focus on the localization of HRas and its minimal anchoring domain, CAAX. We demonstrate the existence of a complex partitioning behavior, where small domains coexist with larger ones. The protein content in these domains varied from two molecules to tens of molecules. We found that 40% of CAAX and 60% of HRas were localized in domains. Subsequently, we were able to manipulate protein distributions by inducing coalescence of supposedly cholesterol-enriched domains. Clustering resulted in an increase of the localized fraction by 15%. 相似文献
107.
108.
Andreas Herchenhan Franziska Uhlenbrock Pernilla Eliasson MaryAnn Weis David Eyre Karl E. Kadler S. Peter Magnusson Michael Kjaer 《The Journal of biological chemistry》2015,290(26):16440-16450
Lysyl oxidases (LOXs) are a family of copper-dependent oxido-deaminases that can modify the side chain of lysyl residues in collagen and elastin, thereby leading to the spontaneous formation of non-reducible aldehyde-derived interpolypeptide chain cross-links. The consequences of LOX inhibition in producing lathyrism are well documented, but the consequences on collagen fibril formation are less clear. Here we used β-aminoproprionitrile (BAPN) to inhibit LOX in tendon-like constructs (prepared from human tenocytes), which are an experimental model of cell-mediated collagen fibril formation. The improvement in structure and strength seen with time in control constructs was absent in constructs treated with BAPN. As expected, BAPN inhibited the formation of aldimine-derived cross-links in collagen, and the constructs were mechanically weak. However, an unexpected finding was that BAPN treatment led to structurally abnormal collagen fibrils with irregular profiles and widely dispersed diameters. Of special interest, the abnormal fibril profiles resembled those seen in some Ehlers-Danlos Syndrome phenotypes. Importantly, the total collagen content developed normally, and there was no difference in COL1A1 gene expression. Collagen type V, decorin, fibromodulin, and tenascin-X proteins were unaffected by the cross-link inhibition, suggesting that LOX regulates fibrillogenesis independently of these molecules. Collectively, the data show the importance of LOX for the mechanical development of early collagenous tissues and that LOX is essential for correct collagen fibril shape formation. 相似文献
109.
Martin Mehnert Franziska Sommermeyer Maren Berger Sathish Kumar Lakshmipathy Robert Gauss Markus Aebi Ernst Jarosch Thomas Sommer 《Molecular biology of the cell》2015,26(2):185-194
Misfolded proteins of the secretory pathway are extracted from the endoplasmic reticulum (ER), polyubiquitylated by a protein complex termed the Hmg-CoA reductase degradation ligase (HRD-ligase), and degraded by cytosolic 26S proteasomes. This process is termed ER-associated protein degradation (ERAD). We previously showed that the membrane protein Der1, which is a subunit of the HRD-ligase, is involved in the export of aberrant polypeptides from the ER. Unexpectedly, we also uncovered a close spatial proximity of Der1 and the substrate receptor Hrd3 in the ER lumen. We report here on a mutant Hrd3KR that is selectively defective for ERAD of soluble proteins. Hrd3KR displays subtle structural changes that affect its positioning toward Der1. Furthermore, increased quantities of the ER-resident Hsp70-type chaperone Kar2 and the Hsp40-type cochaperone Scj1 bind to Hrd3KR. Of note, deletion of SCJ1 impairs ERAD of model substrates and causes the accumulation of client proteins at Hrd3. Our data imply a function of Scj1 in the removal of malfolded proteins from the receptor Hrd3, which facilitates their delivery to downstream-acting components like Der1. 相似文献
110.
Pablo Moreno Stephan Beisken Bhavana Harsha Venkatesh Muthukrishnan Ilinca Tudose Adriano Dekker Stefanie Dornfeldt Franziska Taruttis Ivo Grosse Janna Hastings Steffen Neumann Christoph Steinbeck 《BMC bioinformatics》2015,16(1)