全文获取类型
收费全文 | 4879篇 |
免费 | 385篇 |
国内免费 | 256篇 |
出版年
2024年 | 6篇 |
2023年 | 54篇 |
2022年 | 116篇 |
2021年 | 230篇 |
2020年 | 159篇 |
2019年 | 191篇 |
2018年 | 185篇 |
2017年 | 115篇 |
2016年 | 214篇 |
2015年 | 304篇 |
2014年 | 326篇 |
2013年 | 350篇 |
2012年 | 427篇 |
2011年 | 405篇 |
2010年 | 232篇 |
2009年 | 225篇 |
2008年 | 273篇 |
2007年 | 245篇 |
2006年 | 201篇 |
2005年 | 156篇 |
2004年 | 149篇 |
2003年 | 146篇 |
2002年 | 117篇 |
2001年 | 89篇 |
2000年 | 81篇 |
1999年 | 64篇 |
1998年 | 28篇 |
1997年 | 41篇 |
1996年 | 51篇 |
1995年 | 28篇 |
1994年 | 26篇 |
1993年 | 23篇 |
1992年 | 45篇 |
1991年 | 29篇 |
1990年 | 21篇 |
1989年 | 18篇 |
1988年 | 23篇 |
1987年 | 18篇 |
1986年 | 13篇 |
1985年 | 13篇 |
1984年 | 8篇 |
1983年 | 17篇 |
1982年 | 9篇 |
1981年 | 8篇 |
1980年 | 5篇 |
1977年 | 4篇 |
1975年 | 4篇 |
1974年 | 3篇 |
1973年 | 3篇 |
1965年 | 3篇 |
排序方式: 共有5520条查询结果,搜索用时 46 毫秒
141.
Roy C. K. Kong Emma J. Petrie Biswaranjan Mohanty Jason Ling Jeremy C. Y. Lee Paul R. Gooley Ross A. D. Bathgate 《The Journal of biological chemistry》2013,288(39):28138-28151
The peptide hormone relaxin is showing potential as a treatment for acute heart failure. Although it is known that relaxin mediates its actions through the G protein-coupled receptor relaxin family peptide receptor 1 (RXFP1), little is known about the molecular mechanisms by which relaxin binding results in receptor activation. Previous studies have highlighted that the unique N-terminal low density lipoprotein class A (LDLa) module of RXFP1 is essential for receptor activation, and it has been hypothesized that this module is the true “ligand” of the receptor that directs the conformational changes necessary for G protein coupling. In this study, we confirmed that an RXFP1 receptor lacking the LDLa module binds ligand normally but cannot signal through any characterized G protein-coupled receptor signaling pathway. Furthermore, we comprehensively examined the contributions of amino acids in the LDLa module to RXFP1 activity using both gain-of-function and loss-of-function mutational analysis together with NMR structural analysis of recombinant LDLa modules. Gain-of-function studies with an inactive RXFP1 chimera containing the LDLa module of the human LDL receptor (LB2) demonstrated two key N-terminal regions of the module that were able to rescue receptor signaling. Loss-of-function mutations of residues in these regions demonstrated that Leu-7, Tyr-9, and Lys-17 all contributed to the ability of the LDLa module to drive receptor activation, and judicious amino acid substitutions suggested this involves hydrophobic interactions. Our results demonstrate that these key residues contribute to interactions driving the active receptor conformation, providing further evidence of a unique mode of G protein-coupled receptor activation. 相似文献
142.
143.
Je Yeong Ko Kyung Hyun Yoo Seon Ah Song Do Yeon Kim Hyun Kyung Kong Curie Ahn Han Woong Lee Duk-Hee Kang Goo Taeg Oh Jong Hoon Park 《The Journal of biological chemistry》2013,288(9):6488-6497
Cilia in ciliated cells consist of protruding structures that sense mechanical and chemical signals from the extracellular environment. Cilia are assembled with variety molecules via a process known as intraflagellar transport (IFT). What controls the length of cilia in ciliated cells is critical to understand ciliary disease such as autosomal dominant polycystic kidney disease, which involves abnormally short cilia. But this control mechanism is not well understood. Previously, multiple tubular cysts have been observed in the kidneys of max-interacting protein 1 (Mxi1)-deficient mice aged 6 months or more. Here, we clarified the relationship between Mxi1 inactivation and cilia disassembly. Cilia phenotypes were observed in kidneys of Mxi1-deficient mice using scanning electron microscopy to elucidate the effect of Mxi1 on renal cilia phenotype, and cilia disassembly was observed in Mxi1-deficient kidney. In addition, genes related to cilia were validated in vitro and in vivo using quantitative PCR, and Ift20 was selected as a candidate gene in this study. The length of cilium decreased, and p-ERK level induced by a cilia defect increased in kidneys of Mxi1-deficient mice. Ciliogenesis of Mxi1-deficient mouse embryonic fibroblasts (MEFs) decreased, and this abnormality was restored by Mxi1 transfection in Mxi1-deficient MEFs. We confirmed that ciliogenesis and Ift20 expression were regulated by Mxi1 in vitro. We also determined that Mxi1 regulates Ift20 promoter activity via Ets-1 binding to the Ift20 promoter. These results indicate that inactivating Mxi1 induces ciliary defects in polycystic kidney. 相似文献
144.
Physiological and molecular determinants of embryo implantation 总被引:1,自引:0,他引:1
Shuang Zhang Haiyan Lin Shuangbo Kong Shumin Wang Hongmei Wang Haibin Wang D. Randall Armant 《Molecular aspects of medicine》2013
Embryo implantation involves the intimate interaction between an implantation-competent blastocyst and a receptive uterus, which occurs in a limited time period known as the window of implantation. Emerging evidence shows that defects originating during embryo implantation induce ripple effects with adverse consequences on later gestation events, highlighting the significance of this event for pregnancy success. Although a multitude of cellular events and molecular pathways involved in embryo–uterine crosstalk during implantation have been identified through gene expression studies and genetically engineered mouse models, a comprehensive understanding of the nature of embryo implantation is still missing. This review focuses on recent progress with particular attention to physiological and molecular determinants of blastocyst activation, uterine receptivity, blastocyst attachment and uterine decidualization. A better understanding of underlying mechanisms governing embryo implantation should generate new strategies to rectify implantation failure and improve pregnancy rates in women. 相似文献
145.
146.
Xian-Ling Ji Mei Yan Zai-Dong Yang An-Fei Li Ling-Rang Kong 《Indian journal of microbiology》2013,53(4):400-409
Fusarium head blight, caused predominately by Fusarium graminearum, is one of the most destructive diseases of wheat (Triticum aestivum L.) worldwide. To characterize the profile of proteins secreted by F. graminearum, the extracellular proteins were collectively obtained from F. graminearum culture supernatants and evaluated using one-dimensional SDS-PAGE and liquid chromatography-tandem mass spectrometry. A total of 87 proteins have been identified, of which 63 were predicted as secretory proteins including those with known functions. Meanwhile, 20 proteins that are not homologous to genomic sequences with known functions have also been detected. Some of the identified proteins are possible virulence factors and may play extracellular roles during F. graminearum infection. This study provides a valuable dataset of F. graminearum extracellular proteins, and a better understanding of the virulence mechanisms of the pathogen. 相似文献
147.
148.
Bo Sun XiangHui Yu Wei Kong Shiyang Sun Ping Yang Changlin Zhu Haihong Zhang Yongge Wu Yan Chen Yuhua Shi Xizhen Zhang Chunlai Jiang 《Applied microbiology and biotechnology》2013,97(3):1063-1070
A process for human influenza H1N1 virus vaccine production from Madin–Darby canine kidney (MDCK) cells using a novel packed-bed bioreactor is described in this report. The mini-bioreactor was used to study the relationship between cell density and glucose consumption rate and to optimize the infection parameters of the influenza H1N1 virus (A/New Caledonia/20/99). The MDCK cell culture and virus infection were then monitored in a disposable perfusion bioreactor (AmProtein Current Perfusion Bioreactor) with proportional–integral–derivative control of pH, dissolved O2 (DO), agitation, and temperature. During 6 days of culture, the total cell number increased from 2.0?×?109 to 3.2?×?1010 cells. The maximum virus titers of 768 hemagglutinin units/100 μL and 7.8?×?107 50 % tissue culture infectious doses/mL were obtained 3 days after infection. These results demonstrate that using a disposable perfusion bioreactor for large-scale cultivation of MDCK cells, which allows for the control of DO, pH, and other conditions, is a convenient and stable platform for industrial-scale production of influenza vaccines. 相似文献
149.
The factors responsible for the regulation of regenerative calcium-induced calcium release (CICR) during Ca2+ spark evolution remain unclear. Cardiac ryanodine receptor (RyR) gating in rats and sheep was recorded at physiological Ca2+, Mg2+, and ATP levels and incorporated into a 3D model of the cardiac dyad, which reproduced the time course of Ca2+ sparks, Ca2+ blinks, and Ca2+ spark restitution. The termination of CICR by induction decay in the model principally arose from the steep Ca2+ dependence of RyR closed time, with the measured sarcoplasmic reticulum (SR) lumen Ca2+ dependence of RyR gating making almost no contribution. The start of CICR termination was strongly dependent on the extent of local depletion of junctional SR Ca2+, as well as the time course of local Ca2+ gradients within the junctional space. Reducing the dimensions of the dyad junction reduced Ca2+ spark amplitude by reducing the strength of regenerative feedback within CICR. A refractory period for Ca2+ spark initiation and subsequent Ca2+ spark amplitude restitution arose from 1), the extent to which the regenerative phase of CICR can be supported by the partially depleted junctional SR, and 2), the availability of releasable Ca2+ in the junctional SR. The physical organization of RyRs within the junctional space had minimal effects on Ca2+ spark amplitude when more than nine RyRs were present. Spark amplitude had a nonlinear dependence on RyR single-channel Ca2+ flux, and was approximately halved by reducing the flux from 0.6 to 0.2 pA. Although rat and sheep RyRs had quite different Ca2+ sensitivities, Ca2+ spark amplitude was hardly affected. This suggests that moderate changes in RyR gating by second-messenger systems will principally alter the spatiotemporal properties of SR release, with smaller effects on the amount released. 相似文献
150.
Bo Kong Jacqueline V. Shanks R. Dennis Vigil 《Biotechnology and bioengineering》2013,110(8):2140-2149
The rate of production of algal biomass in optically dense photobioreactors depends crucially on the temporal light exposure of microorganisms, which in turn is determined by fluid flow patterns and the quantity and spatial distribution of photosynthetically active radiation. In this report it is demonstrated that highly organized and robust toroidal flow structures known as Taylor vortices cause significant increases in the rate of biomass production, efficiency of light utilization, and CO2 uptake, and these effects become more pronounced at higher Reynolds numbers. In light of these findings and previously reported experiments using Taylor vortex flow to culture algae, it is argued that the flashing light effect, rather than mass transport effects, is responsible for the observed increases in the rate of photosynthesis. Biotechnol. Bioeng. 2013; 110: 2140–2149. © 2013 Wiley Periodicals, Inc. 相似文献