全文获取类型
收费全文 | 16213篇 |
免费 | 1508篇 |
国内免费 | 1841篇 |
出版年
2024年 | 49篇 |
2023年 | 217篇 |
2022年 | 533篇 |
2021年 | 783篇 |
2020年 | 602篇 |
2019年 | 708篇 |
2018年 | 699篇 |
2017年 | 558篇 |
2016年 | 704篇 |
2015年 | 1012篇 |
2014年 | 1248篇 |
2013年 | 1317篇 |
2012年 | 1523篇 |
2011年 | 1419篇 |
2010年 | 906篇 |
2009年 | 798篇 |
2008年 | 966篇 |
2007年 | 865篇 |
2006年 | 747篇 |
2005年 | 677篇 |
2004年 | 635篇 |
2003年 | 540篇 |
2002年 | 472篇 |
2001年 | 326篇 |
2000年 | 235篇 |
1999年 | 202篇 |
1998年 | 151篇 |
1997年 | 110篇 |
1996年 | 95篇 |
1995年 | 76篇 |
1994年 | 72篇 |
1993年 | 47篇 |
1992年 | 43篇 |
1991年 | 43篇 |
1990年 | 29篇 |
1989年 | 30篇 |
1988年 | 25篇 |
1987年 | 23篇 |
1986年 | 11篇 |
1985年 | 9篇 |
1984年 | 9篇 |
1983年 | 11篇 |
1982年 | 8篇 |
1981年 | 7篇 |
1980年 | 2篇 |
1979年 | 5篇 |
1978年 | 5篇 |
1970年 | 1篇 |
1965年 | 4篇 |
1950年 | 2篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
991.
Longhua Liu Louise D. Zheng Peng Zou Joseph Brooke Cayleen Smith Yun Chau Long 《Cell cycle (Georgetown, Tex.)》2016,15(15):2033-2041
Obesity and related metabolic disorders constitute one of the most pressing heath concerns worldwide. Increased adiposity is linked to autophagy upregulation in adipose tissues. However, it is unknown how autophagy is upregulated and contributes to aberrant adiposity. Here we show a FoxO1-autophagy-FSP27 axis that regulates adipogenesis and lipid droplet (LD) growth in adipocytes. Adipocyte differentiation was associated with upregulation of autophagy and fat specific protein 27 (FSP27), a key regulator of adipocyte maturation and expansion by promoting LD formation and growth. However, FoxO1 specific inhibitor AS1842856 potently suppressed autophagy, FSP27 expression, and adipocyte differentiation. In terminally differentiated adipocytes, AS1842856 significantly reduced FSP27 level and LD size, which was recapitulated by autophagy inhibitors (bafilomycin-A1 and leupeptin, BL). Similarly, AS1842856 and BL dampened autophagy activity and FSP27 expression in explant cultures of white adipose tissue. To our knowledge, this is the first study addressing FoxO1 in the regulation of adipose autophagy, shedding light on the mechanism of increased autophagy and adiposity in obese individuals. Given that adipogenesis and adipocyte expansion contribute to aberrant adiposity, targeting the FoxO1-autophagy-FSP27 axis may lead to new anti-obesity options. 相似文献
992.
993.
Lifang Zou Guihua Tu Wei Xie Shiyao Wen Qiuyu Xie Shuangmei Liu Guilin Li Yun Gao Hong Xu Shouyu Wang Yun Xue Bing Wu Qiulan Lv Mofeng Ying Xi Zhang Shangdong Liang 《Purinergic signalling》2016,12(1):127-137
Adenosine triphosphate (ATP) acts on P2X receptors to initiate signal transmission. P2X7 receptors play a role in the pathophysiological process of myocardial ischemic injury. Long noncoding RNAs (lncRNAs) participate in numerous biological functions independent of protein translation. LncRNAs are implicated in nervous system diseases. This study investigated the effects of NONRATT021972 small interference RNA (siRNA) on the pathophysiologic processes mediated by P2X7 receptors in stellate ganglia (SG) after myocardial ischemic injury. Our results demonstrated that the expression of NONRATT021972 in SG was significantly higher in the myocardial ischemic (MI) group than in the control group. Treatment of MI rats with NONRATT021972 siRNA, the P2X7 antagonist brilliant blue G (BBG), or P2X7 siRNA improved the histology of injured ischemic cardiac tissues and decreased the elevated concentrations of serum myocardial enzymes, creatine kinase (CK), CK isoform MB (CK-MB), lactate dehydrogenase (LDH) and aspartate aminotransferase (AST) compared to the MI rats. NONRATT021972 siRNA, BBG, or P2X7 siRNA treatment in MI rats decreased the expression levels of P2X7 immunoreactivity, P2X7 messenger RNA (mRNA), and P2X7 protein, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and phosphorylated p38 mitogen-activated protein kinase (p38 MAPK) in the SG compared to MI rats. NONRATT021972 siRNA treatment prevented the pathophysiologic processes mediated by P2X7 receptors in the SG after myocardial ischemic injury. 相似文献
994.
High glucose concentration induces endothelial cell proliferation by regulating cyclin‐D2‐related miR‐98
下载免费PDF全文
![点击此处可从《Journal of cellular and molecular medicine》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Xin‐Xin Li Yue‐Mei Liu You‐Jie Li Ning Xie Yun‐Fei Yan Yong‐Liang Chi Ling Zhou Shu‐Yang Xie Ping‐Yu Wang 《Journal of cellular and molecular medicine》2016,20(6):1159-1169
Cyclin D2 is involved in the pathology of vascular complications of type 2 diabetes mellitus (T2DM). This study investigated the role of cyclin‐D2‐regulated miRNAs in endothelial cell proliferation of T2DM. Results showed that higher glucose concentration (4.5 g/l) significantly promoted the proliferation of rat aortic endothelial cells (RAOECs), and significantly increased the expression of cyclin D2 and phosphorylation of retinoblastoma 1 (p‐RB1) in RAOECs compared with those under low glucose concentration. The cyclin D2‐3′ untranslated region is targeted by miR‐98, as demonstrated by miRNA analysis software. Western blot also confirmed that cyclin D2 and p‐RB1 expression was regulated by miR‐98. The results indicated that miR‐98 treatment can induce RAOEC apoptosis. The suppression of RAOEC growth by miR‐98 might be related to regulation of Bcl‐2, Bax and Caspase 9 expression. Furthermore, the expression levels of miR‐98 decreased in 4.5 g/l glucose‐treated cells compared with those treated by low glucose concentration. Similarly, the expression of miR‐98 significantly decreased in aortas of established streptozotocin (STZ)‐induced diabetic rat model compared with that in control rats; but cyclin D2 and p‐RB1 levels remarkably increased in aortas of STZ‐induced diabetic rats compared with those in healthy control rats. In conclusion, this study demonstrated that high glucose concentration induces cyclin D2 up‐regulation and miR‐98 down‐regulation in the RAOECs. By regulating cyclin D2, miR‐98 can inhibit human endothelial cell growth, thereby providing novel therapeutic targets for vascular complication of T2DM. 相似文献
995.
George G. Harrigan Tyamagondlu V. Venkatesh Mark Leibman Jonathan Blankenship Timothy Perez Steven Halls Alexander W. Chassy Oliver Fiehn Yun Xu Royston Goodacre 《Metabolomics : Official journal of the Metabolomic Society》2016,12(5):82
Introduction
Past studies on plant metabolomes have highlighted the influence of growing environments and varietal differences in variation of levels of metabolites yet there remains continued interest in evaluating the effect of genetic modification (GM).Objectives
Here we test the hypothesis that metabolomics differences in grain from maize hybrids derived from a series of GM (NK603, herbicide tolerance) inbreds and corresponding negative segregants can arise from residual genetic variation associated with backcrossing and that the effect of insertion of the GM trait is negligible.Methods
Four NK603-positive and negative segregant inbred males were crossed with two different females (testers). The resultant hybrids, as well as conventional comparator hybrids, were then grown at three replicated field sites in Illinois, Minnesota, and Nebraska during the 2013 season. Metabolomics data acquisition using gas chromatography–time of flight-mass spectrometry (GC–TOF-MS) allowed the measurement of 367 unique metabolite features in harvested grain, of which 153 were identified with small molecule standards. Multivariate analyses of these data included multi-block principal component analysis and ANOVA-simultaneous component analysis. Univariate analyses of all 153 identified metabolites was conducted based on significance testing (α = 0.05), effect size evaluation (assessing magnitudes of differences), and variance component analysis.Results
Results demonstrated that the largest effects on metabolomic variation were associated with different growing locations and the female tester. They further demonstrated that differences observed between GM and non-GM comparators, even in stringent tests utilizing near-isogenic positive and negative segregants, can simply reflect minor genomic differences associated with conventional back-crossing practices.Conclusion
The effect of GM on metabolomics variation was determined to be negligible and supports that there is no scientific rationale for prioritizing GM as a source of variation.996.
997.
Mechanism and rate constants of the Cdc42 GTPase binding with intrinsically disordered effectors
下载免费PDF全文
![点击此处可从《Proteins》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Intrinsically disordered proteins (IDPs) are often involved in signaling and regulatory functions, through binding to cellular targets. Many IDPs undergo disorder‐to‐order transitions upon binding. Both the binding mechanisms and the magnitudes of the binding rate constants can have functional importance. Previously we have found that the coupled binding and folding of any IDP generally follows a sequential mechanism that we term dock‐and‐coalesce, whereby one segment of the IDP first docks to its subsite on the target surface and the remaining segments subsequently coalesce around their respective subsites. Here we applied our TransComp method within the framework of the dock‐and‐coalesce mechanism to dissect the binding kinetics of two Rho‐family GTPases, Cdc42 and TC10, with two intrinsically disordered effectors, WASP and Pak1. TransComp calculations identified the basic regions preceding the GTPase binding domains (GBDs) of the effectors as the docking segment. For Cdc42 binding with both WASP and Pak1, the calculated docking rate constants are close to the observed overall binding rate constants, suggesting that basic‐region docking is the rate‐limiting step and subsequent conformational coalescence of the GBDs on the Cdc42 surface is fast. The possibility that conformational coalescence of the WASP GBD on the TC10 surface is slow warrants further experimental investigation. The account for the differences in binding rate constants among the three GTPase‐effector systems and mutational effects therein yields deep physical and mechanistic insight into the binding processes. Our approach may guide the selection of mutations that lead to redesigned binding pathways. Proteins 2016; 84:674–685. © 2016 Wiley Periodicals, Inc. 相似文献
998.
Phylogeny of Impatiens (Balsaminaceae): integrating molecular and morphological evidence into a new classification
下载免费PDF全文
![点击此处可从《Cladistics : the international journal of the Willi Hennig Society》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Sheng‐Xiang Yu Steven B. Janssens Xiang‐Yun Zhu Magnus Lidén Tian‐Gang Gao Wei Wang 《Cladistics : the international journal of the Willi Hennig Society》2016,32(2):179-197
Impatiens L. is one of the largest angiosperm genera, containing over 1000 species, and is notorious for its taxonomic difficulty. Here, we present, to our knowledge, the most comprehensive phylogenetic analysis of the genus to date based on a total evidence approach. Forty‐six morphological characters, mainly obtained from our own investigations, are combined with sequence data from three genetic regions, including nuclear ribosomal ITS and plastid atpB‐rbcL and trnL‐F. We include 150 Impatiens species representing all clades recovered by previous phylogenetic analyses as well as three outgroups. Maximum‐parsimony and Bayesian inference methods were used to infer phylogenetic relationships. Our analyses concur with previous studies, but in most cases provide stronger support. Impatiens splits into two major clades. For the first time, we report that species with three‐colpate pollen and four carpels form a monophyletic group (clade I). Within clade II, seven well‐supported subclades are recognized. Within this phylogenetic framework, character evolution is reconstructed, and diagnostic morphological characters for different clades and subclades are identified and discussed. Based on both morphological and molecular evidence, a new classification outline is presented, in which Impatiens is divided into two subgenera, subgen. Clavicarpa and subgen. Impatiens; the latter is further subdivided into seven sections. 相似文献
999.
1000.