全文获取类型
收费全文 | 3743篇 |
免费 | 304篇 |
专业分类
4047篇 |
出版年
2024年 | 3篇 |
2023年 | 37篇 |
2022年 | 78篇 |
2021年 | 155篇 |
2020年 | 83篇 |
2019年 | 100篇 |
2018年 | 118篇 |
2017年 | 101篇 |
2016年 | 138篇 |
2015年 | 244篇 |
2014年 | 262篇 |
2013年 | 272篇 |
2012年 | 444篇 |
2011年 | 359篇 |
2010年 | 210篇 |
2009年 | 178篇 |
2008年 | 252篇 |
2007年 | 233篇 |
2006年 | 168篇 |
2005年 | 153篇 |
2004年 | 112篇 |
2003年 | 106篇 |
2002年 | 85篇 |
2001年 | 21篇 |
2000年 | 14篇 |
1999年 | 21篇 |
1998年 | 18篇 |
1997年 | 7篇 |
1996年 | 5篇 |
1995年 | 4篇 |
1994年 | 3篇 |
1993年 | 7篇 |
1992年 | 7篇 |
1991年 | 3篇 |
1990年 | 4篇 |
1988年 | 2篇 |
1987年 | 2篇 |
1986年 | 3篇 |
1983年 | 2篇 |
1982年 | 2篇 |
1981年 | 3篇 |
1979年 | 4篇 |
1976年 | 5篇 |
1974年 | 2篇 |
1971年 | 2篇 |
1960年 | 1篇 |
1955年 | 1篇 |
1934年 | 1篇 |
1933年 | 2篇 |
1932年 | 1篇 |
排序方式: 共有4047条查询结果,搜索用时 11 毫秒
101.
Giulia C. Minetti Jerome N. Feige Florian Bombard Annabelle Heier Fredric Morvan Bernd Nürnberg Veronika Leiss Lutz Birnbaumer David J. Glass Mara Fornaro 《Molecular and cellular biology》2014,34(4):619-630
We have previously shown that activation of Gαi2, an α subunit of the heterotrimeric G protein complex, induces skeletal muscle hypertrophy and myoblast differentiation. To determine whether Gαi2 is required for skeletal muscle growth or regeneration, Gαi2-null mice were analyzed. Gαi2 knockout mice display decreased lean body mass, reduced muscle size, and impaired skeletal muscle regeneration after cardiotoxin-induced injury. Short hairpin RNA (shRNA)-mediated knockdown of Gαi2 in satellite cells (SCs) leads to defective satellite cell proliferation, fusion, and differentiation ex vivo. The impaired differentiation is consistent with the observation that the myogenic regulatory factors MyoD and Myf5 are downregulated upon knockdown of Gαi2. Interestingly, the expression of microRNA 1 (miR-1), miR-27b, and miR-206, three microRNAs that have been shown to regulate SC proliferation and differentiation, is increased by a constitutively active mutant of Gαi2 [Gαi2(Q205L)] and counterregulated by Gαi2 knockdown. As for the mechanism, this study demonstrates that Gαi2(Q205L) regulates satellite cell differentiation into myotubes in a protein kinase C (PKC)- and histone deacetylase (HDAC)-dependent manner. 相似文献
102.
Andreas Obermeier Jochen Schneider Steffen Wehner Florian Dominik Matl Matthias Schieker Rüdiger von Eisenhart-Rothe Axel Stemberger Rainer Burgkart 《PloS one》2014,9(7)
Sutures can cause challenging surgical site infections, due to capillary effects resulting in bacteria permeating wounds. Anti-microbial sutures may avoid these complications by inhibiting bacterial pathogens. Recently, first triclosan-resistances were reported and therefore alternative substances are becoming clinically relevant. As triclosan alternative chlorhexidine, the “gold standard” in oral antiseptics was used. The aim of the study was to optimize novel slow release chlorhexidine coatings based on fatty acids in surgical sutures, to reach a high anti-microbial efficacy and simultaneously high biocompatibility. Sutures were coated with chlorhexidine laurate and chlorhexidine palmitate solutions leading to 11, 22 or 33 µg/cm drug concentration per length. Drug release profiles were determined in aqueous elutions. Antibacterial efficacy against Staphylococcus aureus was assessed in agar diffusion tests. Biocompatibility was evaluated via established cytotoxicity assay (WST-1). A commercially triclosan-containing suture (Vicryl Plus), was used as anti-microbial reference. All coated sutures fulfilled European Pharmacopoeia required tensile strength and proved continuous slow drug release over 96 hours without complete wash out of the coated drug. High anti-microbial efficacy for up to 5 days was observed. Regarding biocompatibility, sutures using 11 µg/cm drug content displayed acceptable cytotoxic levels according to ISO 10993-5. The highest potential for human application were shown by the 11 µg/cm chlorhexidine coated sutures with palmitic acid. These novel coated sutures might be alternatives to already established anti-microbial sutures such as Vicryl Plus in case of triclosan-resistance. Chlorhexidine is already an established oral antiseptic, safety and efficacy should be proven for clinical applications in anti-microbial sutures. 相似文献
103.
Ahmad Almilaji Tatsiana Pakladok Carlos Mu?oz Bernat Elvira Mentor Sopjani Florian Lang 《Channels (Austin, Tex.)》2014,8(3):222-229
Klotho is a transmembrane protein expressed primarily in kidney, parathyroid gland, and choroid plexus. The extracellular domain could be cleaved off and released into the systemic circulation. Klotho is in part effective as β-glucuronidase regulating protein stability in the cell membrane. Klotho is a major determinant of aging and life span. Overexpression of Klotho increases and Klotho deficiency decreases life span. Klotho deficiency may further result in hearing loss and cardiac arrhythmia. The present study explored whether Klotho modifies activity and protein abundance of KCNQ1/KCNE1, a K+ channel required for proper hearing and cardiac repolarization. To this end, cRNA encoding KCNQ1/KCNE1 was injected in Xenopus oocytes with or without additional injection of cRNA encoding Klotho. KCNQ1/KCNE1 expressing oocytes were treated with human recombinant Klotho protein (30 ng/ml) for 24 h. Moreover, oocytes which express both KCNQ1/KCNE1 and Klotho were treated with 10 µM DSAL (D-saccharic acid-1,4-lactone), a β-glucuronidase inhibitor. The KCNQ1/KCNE1 depolarization-induced current (IKs) was determined utilizing dual electrode voltage clamp, while KCNQ1/KCNE1 protein abundance in the cell membrane was visualized utilizing specific antibody binding and quantified by chemiluminescence. KCNQ1/KCNE1 channel activity and KCNQ1/KCNE1 protein abundance were upregulated by coexpression of Klotho. The effect was mimicked by treatment with human recombinant Klotho protein (30 ng/ml) and inhibited by DSAL (10 µM). In conclusion, Klotho upregulates KCNQ1/KCNE1 channel activity by 'mainly' enhancing channel protein abundance in the plasma cell membrane, an effect at least partially mediated through the β-glucuronidase activity of Klotho protein. 相似文献
104.
Daniel O. Frank J?rn Dengjel Florian Wilfling Vera Kozjak-Pavlovic Georg H?cker Arnim Weber 《PloS one》2015,10(4)
The pro-apoptotic Bcl-2-family protein Bim belongs to the BH3-only proteins known as initiators of apoptosis. Recent data show that Bim is constitutively inserted in the outer mitochondrial membrane via a C-terminal transmembrane anchor from where it can activate the effector of cytochrome c-release, Bax. To identify regulators of Bim-activity, we conducted a search for proteins interacting with Bim at mitochondria. We found an interaction of Bim with Tom70, Tom20 and more weakly with Tom40, all components of the Translocase of the Outer Membrane (TOM). In vitro import assays performed on tryptically digested yeast mitochondria showed reduced Bim insertion into the outer mitochondrial membrane (OMM) indicating that protein receptors may be involved in the import process. However, RNAi against components of TOM (Tom40, Tom70, Tom22 or Tom20) by siRNA, individually or in combination, did not consistently change the amount of Bim on HeLa mitochondria, either at steady state or upon de novo-induction. In support of this, the individual or combined knock-downs of TOM receptors also failed to alter the susceptibility of HeLa cells to Bim-induced apoptosis. In isolated yeast mitochondria, lack of Tom70 or the TOM-components Tom20 or Tom22 alone did not affect the import of Bim into the outer mitochondrial membrane. In yeast, expression of Bim can sensitize the cells to Bax-dependent killing. This sensitization was unaffected by the absence of Tom70 or by an experimental reduction in Tom40. Although thus the physiological role of the Bim-TOM-interaction remains unclear, TOM complex components do not seem to be essential for Bim insertion into the OMM. Nevertheless, this association should be noted and considered when the regulation of Bim in other cells and situations is investigated. 相似文献
105.
The silver lining of a viral agent: increasing seed yield and harvest index in Arabidopsis by ectopic expression of the potato leaf roll virus movement protein 下载免费PDF全文
Kronberg K Vogel F Rutten T Hajirezaei MR Sonnewald U Hofius D 《Plant physiology》2007,145(3):905-918
Ectopic expression of viral movement proteins (MPs) has previously been shown to alter plasmodesmata (PD) function and carbon partitioning in transgenic plants, giving rise to the view of PD being dynamic and highly regulated structures that allow resource allocation to be adapted to environmental and developmental needs. However, most work has been restricted to solanaceous species and the potential use of MP expression to improve biomass and yield parameters has not been addressed in detail. Here we demonstrate that MP-mediated modification of PD function can substantially alter assimilate allocation, biomass production, and reproductive growth in Arabidopsis (Arabidopsis thaliana). These effects were achieved by constitutive expression of the potato leaf roll virus 17-kD MP (MP17) fused to green fluorescent protein (GFP) in different Arabidopsis ecotypes. The resulting transgenic plants were analyzed for PD localization of the MP17:GFP fusion protein and different lines with low to high expression levels were selected for further analysis. Low-level accumulation of MP17 resulted in enhanced sucrose efflux from source leaves and a considerably increased vegetative biomass production. In contrast, high MP17 levels impaired sucrose export, resulting in source leaf-specific carbohydrate accumulation and a strongly reduced vegetative growth. Surprisingly, later during development the MP17-mediated inhibition of resource allocation was reversed, and final seed yield increased in average up to 30% in different transgenic lines as compared to wild-type plants. This resulted in a strongly improved harvest index. The release of the assimilate export block was paralleled by a reduced PD binding of MP17 in senescing leaves, indicating major structural changes of PD during leaf senescence. 相似文献
106.
107.
Sustainable use of wood may contribute to coping with energy and material resource challenges. The goal of this study is to increase knowledge of the environmental effects of wood use by analyzing the complete value chain of all wooden goods produced or consumed in Switzerland. We start from a material flow analysis of current wood use in Switzerland. Environmental impacts related to the material flows are evaluated using life cycle assessment–based environmental indicators. Regarding climate change, we find an overall average benefit of 0.5 tonnes carbon dioxide equivalent per cubic meter of wood used. High environmental benefits are often achieved when replacing conventional heat production and energy‐consuming materials in construction and furniture. The environmental performance of wood is, however, highly dependent on its use and environmental indicators. To exploit the mitigation potential of wood, we recommend to (1) apply its use where there are high substitution benefits like the replacement of fossil fuels for energy or energy‐intensive building materials, (2) take appropriate measures to minimize negative effects like particulate matter emissions, and (3) keep a systems perspective to weigh effects like substitution and cascading against each other in a comprehensive manner. The results can provide guidance for further in‐depth studies and prospective analyses of wood‐use scenarios. 相似文献
108.
Sopjani M Alesutan I Dërmaku-Sopjani M Gu S Zelenak C Munoz C Velic A Föller M Rosenblatt KP Kuro-o M Lang F 《FEBS letters》2011,585(12):1759-1764
Klotho-hypomorphic (Klotho(hm)) mice suffer from renal salt wasting and hypovolemia despite hyperaldosteronism. The present study explored the effect of Klotho on renal Na(+)/K(+) ATPase activity. According to immunohistochemistry and confocal microscopy Na(+)/K(+) ATPase protein abundance in isolated collecting ducts was lower in Klotho(hm) mice than in their wild type littermates (Klotho(+/+)). Analysis with dual electrode voltage clamp recording showed that expression of Klotho in Xenopus oocytes increased the Na(+)/K(+) ATPase pump current. Treatment of Xenopus oocytes with Klotho protein similarly increased the pump current. In conclusion, Klotho increases the membrane abundance and activity of the Na(+)/K(+) ATPase. Decreased Na(+)/K(+) ATPase activity could thus contribute to the volume-depletion of klotho(hm) mice. 相似文献
109.
110.