全文获取类型
收费全文 | 1196篇 |
免费 | 78篇 |
国内免费 | 1篇 |
出版年
2022年 | 3篇 |
2021年 | 13篇 |
2020年 | 5篇 |
2019年 | 17篇 |
2018年 | 18篇 |
2017年 | 17篇 |
2016年 | 30篇 |
2015年 | 34篇 |
2014年 | 56篇 |
2013年 | 58篇 |
2012年 | 85篇 |
2011年 | 69篇 |
2010年 | 52篇 |
2009年 | 50篇 |
2008年 | 82篇 |
2007年 | 76篇 |
2006年 | 72篇 |
2005年 | 64篇 |
2004年 | 64篇 |
2003年 | 66篇 |
2002年 | 66篇 |
2001年 | 10篇 |
2000年 | 15篇 |
1999年 | 13篇 |
1998年 | 17篇 |
1997年 | 22篇 |
1996年 | 20篇 |
1995年 | 27篇 |
1994年 | 12篇 |
1993年 | 11篇 |
1992年 | 16篇 |
1991年 | 7篇 |
1990年 | 10篇 |
1989年 | 8篇 |
1988年 | 6篇 |
1987年 | 7篇 |
1986年 | 5篇 |
1985年 | 4篇 |
1984年 | 6篇 |
1983年 | 3篇 |
1982年 | 10篇 |
1981年 | 4篇 |
1980年 | 7篇 |
1978年 | 3篇 |
1977年 | 3篇 |
1976年 | 3篇 |
1973年 | 3篇 |
1972年 | 7篇 |
1971年 | 3篇 |
1970年 | 3篇 |
排序方式: 共有1275条查询结果,搜索用时 31 毫秒
101.
102.
103.
Trapani A Denora N Iacobellis G Sitterberg J Bakowsky U Kissel T 《AAPS PharmSciTech》2011,12(4):1302-1311
Brain tumor treatment employing methotrexate (MTX) is limited by the efflux mechanism of Pg-p on the blood–brain barrier.
We aimed to investigate MTX-loaded chitosan or glycol chitosan (GCS) nanoparticles (NPs) in the presence and in the absence
of a coating layer of Tween 80 for brain delivery of MTX. The effect of a low Tween 80 concentration was evaluated. MTX NPs
were formulated following the ionic gelation technique and size and zeta potential measurements were acquired. Transport across
MDCKII-MDR1 monolayer and cytotoxicity studies against C6 glioma cell line were also performed. Cell/particles interaction
was visualized by confocal microscopy. The particles were shown to be cytotoxic against C6 cells line and able to overcome
MDCKII-MDR1 cell barrier. GCS-based NPs were the most cytotoxic NPs. Confocal observations highlighted the internalization
of Tween 80-coated fluorescent NPs more than Tween 80-uncoated NPs. The results suggest that even a low concentration of Tween
80 is sufficient for enhancing the transport of MTX from the NPs across MDCKII-MDR1 cells. The nanocarriers represent a promising
strategy for the administration of MTX to brain tumors which merits further investigations under in vivo conditions. 相似文献
104.
Kempf T Zarbock A Widera C Butz S Stadtmann A Rossaint J Bolomini-Vittori M Korf-Klingebiel M Napp LC Hansen B Kanwischer A Bavendiek U Beutel G Hapke M Sauer MG Laudanna C Hogg N Vestweber D Wollert KC 《Nature medicine》2011,17(5):581-588
Inflammatory cell recruitment after myocardial infarction needs to be tightly controlled to permit infarct healing while avoiding fatal complications such as cardiac rupture. Growth differentiation factor-15 (GDF-15), a transforming growth factor-β (TGF-β)-related cytokine, is induced in the infarcted heart of mice and humans. We show that coronary artery ligation in Gdf15-deficient mice led to enhanced recruitment of polymorphonuclear leukocytes (PMNs) into the infarcted myocardium and an increased incidence of cardiac rupture. Conversely, infusion of recombinant GDF-15 repressed PMN recruitment after myocardial infarction. In vitro, GDF-15 inhibited PMN adhesion, arrest under flow and transendothelial migration. Mechanistically, GDF-15 counteracted chemokine-triggered conformational activation and clustering of β(2) integrins on PMNs by activating the small GTPase Cdc42 and inhibiting activation of the small GTPase Rap1. Intravital microscopy in vivo in Gdf15-deficient mice showed that Gdf-15 is required to prevent excessive chemokine-activated leukocyte arrest on the endothelium. Genetic ablation of β(2) integrins in myeloid cells rescued the mortality of Gdf15-deficient mice after myocardial infarction. To our knowledge, GDF-15 is the first cytokine identified as an inhibitor of PMN recruitment by direct interference with chemokine signaling and integrin activation. Loss of this anti-inflammatory mechanism leads to fatal cardiac rupture after myocardial infarction. 相似文献
105.
Lutz A Nackenhorst U von Lewinski G Windhagen H Floerkemeier T 《Biomechanics and modeling in mechanobiology》2011,10(5):627-640
Numerical investigations with regard to the subtrochanteric fracture risk induced by three alternative methods for the treatment
of femoral head necrosis are outlined in this presentation. The traditional core decompression technique will be compared
with minimal invasive multiple low diameter drillings and the implantation of an innovative tantalum implant. With emphasis
to the newly introduced computational strategies and modeling approaches, the modeling of critical loading conditions as well
as mesh convergence is outlined in detail. In addition to the immediate postoperative fracture risk, the long-term stability
of the different approaches for treating femoral head necrosis is predicted by performing well-established bone remodeling
simulation techniques. The computed results are augmented for results obtained from clinical experience. 相似文献
106.
Plant-based material, protein and biodegradable plastic 总被引:3,自引:0,他引:3
Fibrous proteins from spiders, proteins with synthetic multiple repeats and mammalian structural proteins such as collagen have been produced in transgenic plants. Recent advances in the production of biodegradable plastic in plants also show the potential of molecular farming for research into and production of materials. Selection of a growing variety of such products, optimization of expression, and the development of effective purification strategies will further promote this growing field of biotechnology. 相似文献
107.
A new series of N-linked 5-triazolylmethyl oxazolidinones with varying substitution at the piperazine nitrogen 4-position were synthesized and tested against a panel of Gram-positive and Gram-negative bacteria including clinical isolates. Most of the compounds showed excellent antibacterial activity against susceptible and resistant Gram-positive organisms. One of the compounds showed enhanced antibacterial activity against Moraxella catarrhalis. 相似文献
108.
109.
The objective of this module is to cover ground that was not covered in-depth in any of the other modules, including: scientific misconduct, issues concerning the publication and ownership of research results (authorship guidelines - who is eligible to be considered an author, or contributor to a scientific paper etc.), special problems occurring in social science and epidemiological research, and the problems pertaining to conflicts of interest the various players in biomedical research activities could encounter. 相似文献
110.
DRhoGEF2 regulates actin organization and contractility in the Drosophila blastoderm embryo
下载免费PDF全文
![点击此处可从《The Journal of cell biology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Morphogenesis of the Drosophila melanogaster embryo is associated with a dynamic reorganization of the actin cytoskeleton that is mediated by small GTPases of the Rho family. Often, Rho1 controls different aspects of cytoskeletal function in parallel, requiring a complex level of regulation. We show that the guanine triphosphate (GTP) exchange factor DRhoGEF2 is apically localized in epithelial cells throughout embryogenesis. We demonstrate that DRhoGEF2, which has previously been shown to regulate cell shape changes during gastrulation, recruits Rho1 to actin rings and regulates actin distribution and actomyosin contractility during nuclear divisions, pole cell formation, and cellularization of syncytial blastoderm embryos. We propose that DRhoGEF2 activity coordinates contractile actomyosin forces throughout morphogenesis in Drosophila by regulating the association of myosin with actin to form contractile cables. Our results support the hypothesis that specific aspects of Rho1 function are regulated by specific GTP exchange factors. 相似文献