全文获取类型
收费全文 | 6145篇 |
免费 | 605篇 |
出版年
2023年 | 21篇 |
2022年 | 45篇 |
2021年 | 97篇 |
2020年 | 70篇 |
2019年 | 73篇 |
2018年 | 97篇 |
2017年 | 102篇 |
2016年 | 138篇 |
2015年 | 255篇 |
2014年 | 299篇 |
2013年 | 391篇 |
2012年 | 485篇 |
2011年 | 468篇 |
2010年 | 331篇 |
2009年 | 288篇 |
2008年 | 404篇 |
2007年 | 423篇 |
2006年 | 368篇 |
2005年 | 349篇 |
2004年 | 325篇 |
2003年 | 308篇 |
2002年 | 276篇 |
2001年 | 73篇 |
2000年 | 76篇 |
1999年 | 72篇 |
1998年 | 93篇 |
1997年 | 37篇 |
1996年 | 57篇 |
1995年 | 51篇 |
1994年 | 55篇 |
1993年 | 48篇 |
1992年 | 49篇 |
1991年 | 28篇 |
1990年 | 29篇 |
1989年 | 45篇 |
1988年 | 21篇 |
1987年 | 27篇 |
1986年 | 18篇 |
1985年 | 16篇 |
1984年 | 19篇 |
1982年 | 18篇 |
1981年 | 21篇 |
1979年 | 15篇 |
1977年 | 23篇 |
1976年 | 16篇 |
1975年 | 15篇 |
1974年 | 17篇 |
1973年 | 20篇 |
1972年 | 18篇 |
1971年 | 17篇 |
排序方式: 共有6750条查询结果,搜索用时 156 毫秒
131.
V. P. Edgcomb J. M. Bernhard D. Beaudoin S. Pruss P. V. Welander F. Schubotz S. Mehay A. L. Gillespie R. E. Summons 《Geobiology》2013,11(3):234-251
Microbialites (stromatolites and thrombolites) are mineralized mat structures formed via the complex interactions of diverse microbial‐mat communities. At Highborne Cay, in the Bahamas, the carbonate component of these features is mostly comprised of ooids. These are small, spherical to ellipsoidal grains characterized by concentric layers of calcium carbonate and organic matter and these sand‐sized particles are incorporated with the aid of extra‐cellular polymeric substances (EPS), into the matrix of laminated stromatolites and clotted thrombolite mats. Here, we present a comparison of the bacterial diversity within oolitic sand samples and bacterial diversity previously reported in thrombolitic and stromatolitic mats of Highborne Cay based on analysis of clone libraries of small subunit ribosomal RNA gene fragments and lipid biomarkers. The 16S‐rRNA data indicate that the overall bacterial diversity within ooids is comparable to that found within thrombolites and stromatolites of Highborne Cay, and this significant overlap in taxonomic groups suggests that ooid sands may be a source for much of the bacterial diversity found in the local microbialites. Cyanobacteria were the most diverse taxonomic group detected, followed by Alphaproteobacteria, Gammaproteobacteria, Planctomyces, Deltaproteobacteria, and several other groups also found in mat structures. The distributions of intact polar lipids, the fatty acids derived from them, and bacteriohopanepolyols provide broad general support for the bacterial diversity identified through analysis of nucleic acid clone libraries. 相似文献
132.
133.
John Paul Wanner Roopashree Subbaiah Yelenna Skomorovska-Prokvolit Yousef Shishani Eric Boilard Sujatha Mohan Robert Gillespie Masaru Miyagi Reuben Gobezie 《Arthritis research & therapy》2013,15(6):R180
Introduction
The development of effective treatments for osteoarthritis (OA) has been hampered by a poor understanding of OA at the cellular and molecular levels. Emerging as a disease of the ''whole joint’, the importance of the biochemical contribution of various tissues, including synovium, bone and articular cartilage, has become increasingly significant. Bathing the entire joint structure, the proteomic analysis of synovial fluid (SF) from osteoarthritic shoulders offers a valuable ''snapshot’ of the biologic environment throughout disease progression. The purpose of this study was to identify differentially expressed proteins in early and late shoulder osteoarthritic SF in comparison to healthy SF.Methods
A quantitative 18O labeling proteomic approach was employed to identify the dysregulated SF proteins in early (n = 5) and late (n = 4) OA patients compared to control individuals (n = 5). In addition, ELISA was used to quantify six pro-inflammatory and two anti-inflammatory cytokines.Results
Key results include a greater relative abundance of proteins related to the complement system and the extracellular matrix in SF from both early and late OA. Pathway analyses suggests dysregulation of the acute phase response, liver x receptor/retinoid x receptor (LXR/RXR), complement system and coagulation pathways in both early and late OA. The network related to lipid metabolism was down-regulated in both early and late OA. Inflammatory cytokines including interleukin (IL) 6, IL 8 and IL 18 were up-regulated in early and late OA.Conclusions
The results suggest a dysregulation of wound repair pathways in shoulder OA contributing to the presence of a ''chronic wound’ that progresses irreversibly from early to later stages of OA. Protease inhibitors were downregulated in late OA suggesting uncontrolled proteolytic activity occurring in late OA. These results contribute to the theory that protease inhibitors represent promising therapeutic agents which could limit proteolytic activity that ultimately leads to cartilage destruction. 相似文献134.
135.
136.
137.
Mahban Irandoust Julian Alvarez Zarate Isabelle Hubeek Ellen M. van Beek Karin Schornagel Aart J. F. Broekhuizen Mercan Akyuz Arjan A. van de Loosdrecht Ruud Delwel Peter J. Valk Edwin Sonneveld Pamela Kearns Ursula Creutzig Dirk Reinhardt Eveline S. J. M. de Bont Eva A. Coenen Marry M. van den Heuvel-Eibrink C. Michel Zwaan Gertjan J. L. Kaspers Jacqueline Cloos Timo K. van den Berg 《PloS one》2013,8(1)
Background
Recent studies show the importance of interactions between CD47 expressed on acute myeloid leukemia (AML) cells and the inhibitory immunoreceptor, signal regulatory protein-alpha (SIRPα) on macrophages. Although AML cells express SIRPα, its function has not been investigated in these cells. In this study we aimed to determine the role of the SIRPα in acute myeloid leukemia.Design and Methods
We analyzed the expression of SIRPα, both on mRNA and protein level in AML patients and we further investigated whether the expression of SIRPα on two low SIRPα expressing AML cell lines could be upregulated upon differentiation of the cells. We determined the effect of chimeric SIRPα expression on tumor cell growth and programmed cell death by its triggering with an agonistic antibody in these cells. Moreover, we examined the efficacy of agonistic antibody in combination with established antileukemic drugs.Results
By microarray analysis of an extensive cohort of primary AML samples, we demonstrated that SIRPα is differentially expressed in AML subgroups and its expression level is dependent on differentiation stage, with high levels in FAB M4/M5 AML and low levels in FAB M0–M3. Interestingly, AML patients with high SIRPα expression had a poor prognosis. Our results also showed that SIRPα is upregulated upon differentiation of NB4 and Kasumi cells. In addition, triggering of SIRPα with an agonistic antibody in the cells stably expressing chimeric SIRPα, led to inhibition of growth and induction of programmed cell death. Finally, the SIRPα-derived signaling synergized with the activity of established antileukemic drugs.Conclusions
Our data indicate that triggering of SIRPα has antileukemic effect and may function as a potential therapeutic target in AML. 相似文献138.
139.
Stefanie Bunse Sakshi Garg Stephan Junek Dirk Vogel Nariman Ansari Ernst H. K. Stelzer Erin Schuman 《PloS one》2013,8(12)
Cadherins, Ca2+-dependent adhesion molecules, are crucial for cell-cell junctions and remodeling. Cadherins form inter-junctional lattices by the formation of both cis and trans dimers. Here, we directly visualize and quantify the spatiotemporal dynamics of wild-type and dimer mutant N-cadherin interactions using time-lapse imaging of junction assembly, disassembly and a FRET reporter to assess Ca2+-dependent interactions. A trans dimer mutant (W2A) and a cis mutant (V81D/V174D) exhibited an increased Ca2+-sensitivity for the disassembly of trans dimers compared to the WT, while another mutant (R14E) was insensitive to Ca2+-chelation. Time-lapse imaging of junction assembly and disassembly, monitored in 2D and 3D (using cellular spheroids), revealed kinetic differences in the different mutants as well as different behaviors in the 2D and 3D environment. Taken together, these data provide new insights into the role that the cis and trans dimers play in the dynamic interactions of cadherins. 相似文献
140.
Motivated by recent experimental findings, we propose a novel mechanism of embryonic pattern formation based on coupling of tissue curvature with diffusive signaling by a chemical factor. We derive a new mathematical model using energy minimization approach and show that the model generates a variety of morphogen and curvature patterns agreeing with experimentally observed structures. The mechanism proposed transcends the classical Turing concept which requires interactions between two morphogens with a significantly different diffusivity. Our studies show how biomechanical forces may replace the elusive long-range inhibitor and lead to formation of stable spatially heterogeneous structures without existence of chemical prepatterns. We propose new experimental approaches to decisively test our central hypothesis that tissue curvature and morphogen expression are coupled in a positive feedback loop. 相似文献