全文获取类型
收费全文 | 7053篇 |
免费 | 626篇 |
国内免费 | 1篇 |
专业分类
7680篇 |
出版年
2024年 | 11篇 |
2023年 | 41篇 |
2022年 | 111篇 |
2021年 | 205篇 |
2020年 | 93篇 |
2019年 | 119篇 |
2018年 | 159篇 |
2017年 | 130篇 |
2016年 | 236篇 |
2015年 | 457篇 |
2014年 | 484篇 |
2013年 | 469篇 |
2012年 | 656篇 |
2011年 | 625篇 |
2010年 | 355篇 |
2009年 | 302篇 |
2008年 | 469篇 |
2007年 | 448篇 |
2006年 | 398篇 |
2005年 | 369篇 |
2004年 | 335篇 |
2003年 | 346篇 |
2002年 | 290篇 |
2001年 | 52篇 |
2000年 | 35篇 |
1999年 | 68篇 |
1998年 | 64篇 |
1997年 | 44篇 |
1996年 | 41篇 |
1995年 | 36篇 |
1994年 | 25篇 |
1993年 | 34篇 |
1992年 | 25篇 |
1991年 | 14篇 |
1990年 | 17篇 |
1989年 | 11篇 |
1988年 | 10篇 |
1987年 | 11篇 |
1986年 | 5篇 |
1985年 | 15篇 |
1984年 | 10篇 |
1983年 | 4篇 |
1982年 | 5篇 |
1981年 | 6篇 |
1980年 | 7篇 |
1978年 | 6篇 |
1977年 | 6篇 |
1975年 | 3篇 |
1974年 | 5篇 |
1967年 | 3篇 |
排序方式: 共有7680条查询结果,搜索用时 8 毫秒
171.
Normal enteric nervous system (ENS) development relies on numerous factors, including appropriate migration, proliferation, differentiation, and maturation of neural crest (NC) derivatives. Incomplete rostral to caudal migration of enteric neural crest-derived progenitors (ENPs) down the gut is at least partially responsible for the absence of enteric ganglia that is a hallmark feature of Hirschsprung disease (HSCR). The thought that ganglia proximal to aganglionosis are normal has guided surgical procedures for HSCR patients. However, chronic gastrointestinal dysfunction suffered by a subset of patients after surgery as well as studies in HSCR mouse models suggest that aberrant NC segregation and differentiation may be occurring in ganglionated regions of the intestine. Studies in mouse models that possess enteric ganglia throughout the length of the intestine (non-HSCR) have also found that certain genetic alterations affect neural crest lineage balance and interestingly many of these mutants also have functional gastrointestinal (GI) defects. It is possible that many GI disorders can be explained in part by imbalances in NC-derived lineages. Here we review studies evaluating ENS defects in HSCR and non-HSCR mouse models, concluding with clinical implications while highlighting areas requiring further study. 相似文献
172.
Actin dynamics is important in determining cell shape, tension, and migration. Methods such as fluorescent speckle microscopy and spatial temporal image correlation spectroscopy have been used to capture high-resolution actin turnover dynamics within cells in two dimensions. However, these methods are not directly applicable in 3D due to lower resolution and poor contrast. Here, we propose to capture actin flow in 3D with high spatial-temporal resolution by combining nanoscale precise imaging by rapid beam oscillation and fluctuation spectroscopy techniques. To measure the actin flow along cell protrusions in cell expressing actin-eGFP cultured in a type I collagen matrix, the laser was orbited around the protrusion and its trajectory was modulated in a clover-shaped pattern perpendicularly to the protrusion. Orbits were also alternated at two positions closely spaced along the protrusion axis. The pair cross-correlation function was applied to the fluorescence fluctuation from these two positions to capture the flow of actin. Measurements done on nonmoving cellular protrusion tips showed no pair-correlation at two orbital positions indicating a lack of flow of F-actin bundles. However, in some protrusions, the pair-correlation approach revealed directional flow of F-actin bundles near the protrusion surface with flow rates in the range of ∼1 μm/min, comparable to results in two dimensions using fluorescent speckle microscopy. Furthermore, we found that the actin flow rate is related to the distance to the protrusion tip. We also observed collagen deformation by concomitantly detecting collagen fibers with reflectance detection during these actin motions. The implementation of the nanoscale precise imaging by rapid beam oscillation method with a cloverleaf-shaped trajectory in conjunction with the pair cross-correlation function method provides a quantitative way of capturing dynamic flows and organization of proteins during cell migration in 3D in conditions of poor contrast. 相似文献
173.
Michelle D. Hamilton 《American journal of physical anthropology》2013,152(4):570-570
174.
175.
Elisa Tran Annabelle Chow Takeshi Goda Amy Wong Kim Blakely Michelle Rocha Samira Taeb Van C. Hoang Stanley K. Liu Urban Emmenegger 《Biochemical and biophysical research communications》2013
ATG4B belongs to the autophagin family of cysteine proteases required for autophagy, an emerging target of cancer therapy. Developing pharmacological ATG4B inhibitors is a very active area of research. However, detailed studies on the role of ATG4B during anticancer therapy are lacking. By analyzing PC-3 and C4-2 prostate cancer cells overexpressing dominant negative ATG4BC74Ain vitro and in vivo, we show that the effects of ATG4BC74A are cell type, treatment, and context-dependent. ATG4BC74A expression can either amplify the effects of cytotoxic therapies or contribute to treatment resistance. Thus, the successful clinical application of ATG4B inhibitors will depend on finding predictive markers of response. 相似文献
176.
Discovery of a small-molecule inhibitor and cellular probe of Keap1–Nrf2 protein–protein interaction
Longqin Hu Sadagopan Magesh Lin Chen Lili Wang Timothy A. Lewis Yu Chen Carol Khodier Daigo Inoyama Lesa J. Beamer Thomas J. Emge Jian Shen John E. Kerrigan Ah-Ng Tony Kong Sivaraman Dandapani Michelle Palmer Stuart L. Schreiber Benito Munoz 《Bioorganic & medicinal chemistry letters》2013,23(10):3039-3043
A high-throughput screen (HTS) of the MLPCN library using a homogenous fluorescence polarization assay identified a small molecule as a first-in-class direct inhibitor of Keap1–Nrf2 protein–protein interaction. The HTS hit has three chiral centers; a combination of flash and chiral chromatographic separation demonstrated that Keap1-binding activity resides predominantly in one stereoisomer (SRS)-5 designated as ML334 (LH601A), which is at least 100× more potent than the other stereoisomers. The stereochemistry of the four cis isomers was assigned using X-ray crystallography and confirmed using stereospecific synthesis. (SRS)-5 is functionally active in both an ARE gene reporter assay and an Nrf2 nuclear translocation assay. The stereospecific nature of binding between (SRS)-5 and Keap1 as well as the preliminary but tractable structure–activity relationships support its use as a lead for our ongoing optimization 相似文献
177.
Erin Styles Ji-Young Youn Mojca Mattiazzi Usaj Brenda Andrews 《Philosophical transactions of the Royal Society of London. Series B, Biological sciences》2013,368(1629)
The budding yeast Saccharomyces cerevisiae has been used extensively for the study of cell polarity, owing to both its experimental tractability and the high conservation of cell polarity and other basic biological processes among eukaryotes. The budding yeast has also served as a pioneer model organism for virtually all genome-scale approaches, including functional genomics, which aims to define gene function and biological pathways systematically through the analysis of high-throughput experimental data. Here, we outline the contributions of functional genomics and high-throughput methodologies to the study of cell polarity in the budding yeast. We integrate data from published genetic screens that use a variety of functional genomics approaches to query different aspects of polarity. Our integrated dataset is enriched for polarity processes, as well as some processes that are not intrinsically linked to cell polarity, and may provide new areas for future study. 相似文献
178.
Human sleep‐wake cycles in the high arctic: Effects of unusual photoperiodicity in a natural setting
G. Daniel Steel Michelle Callaway Peter Suedfeld Lawrence Palinkas 《Biological Rhythm Research》2013,44(5):582-592
Abstract Studies of human circadian rhythms are typically conducted in artificial environments that are low in ecological validity. In the current study, six subjects and the field director lived in temporal isolation in a completely natural environment with constant daylight (a high Arctic research camp) for six weeks. Detailed daily sleep logs were kept. In keeping with past findings, five of the six subjects developed a free‐running sleep‐wake cycle longer than 24 hours. Unlike past results, the isolated subjects did not exhibit any synchronicity in their rhythms. There was a high degree of intersubject variability in circadian patterns. The findings have important implications for the comparison of the results of laboratory and field investigations of sleep‐wake cycles. 相似文献
179.
Jianjian Shi Xiangbing Wu Michelle Surma Sasidhar Vemula Lumin Zhang Yu Yang Reuben Kapur Lei Wei 《Cell death & disease》2013,4(2):e483
This study, using mouse embryonic fibroblast (MEF) cells derived from ROCK1−/− and ROCK2−/− mice, is designed to dissect roles for ROCK1 and ROCK2 in regulating actin cytoskeleton reorganization induced by doxorubicin, a chemotherapeutic drug. ROCK1−/− MEFs exhibited improved actin cytoskeleton stability characterized by attenuated periphery actomyosin ring formation and preserved central stress fibers, associated with decreased myosin light chain 2 (MLC2) phosphorylation but preserved cofilin phosphorylation. These effects resulted in a significant reduction in cell shrinkage, detachment, and predetachment apoptosis. In contrast, ROCK2−/− MEFs showed increased periphery membrane folding and impaired cell adhesion, associated with reduced phosphorylation of both MLC2 and cofilin. Treatment with inhibitor of myosin (blebbistatin), inhibitor of actin polymerization (cytochalasin D), and ROCK pan-inhibitor (Y27632) confirmed the contributions of actomyosin contraction and stress fiber instability to stress-induced actin cytoskeleton reorganization. These results support a novel concept that ROCK1 is involved in destabilizing actin cytoskeleton through regulating MLC2 phosphorylation and peripheral actomyosin contraction, whereas ROCK2 is required for stabilizing actin cytoskeleton through regulating cofilin phosphorylation. Consequently, ROCK1 and ROCK2 can be functional different in regulating stress-induced stress fiber disassembly and cell detachment. 相似文献
180.