全文获取类型
收费全文 | 510篇 |
免费 | 21篇 |
专业分类
531篇 |
出版年
2022年 | 5篇 |
2021年 | 9篇 |
2020年 | 6篇 |
2019年 | 5篇 |
2018年 | 9篇 |
2017年 | 8篇 |
2016年 | 13篇 |
2015年 | 19篇 |
2014年 | 21篇 |
2013年 | 24篇 |
2012年 | 31篇 |
2011年 | 35篇 |
2010年 | 22篇 |
2009年 | 17篇 |
2008年 | 17篇 |
2007年 | 19篇 |
2006年 | 36篇 |
2005年 | 19篇 |
2004年 | 19篇 |
2003年 | 24篇 |
2002年 | 23篇 |
2001年 | 10篇 |
2000年 | 8篇 |
1999年 | 8篇 |
1998年 | 3篇 |
1997年 | 4篇 |
1995年 | 3篇 |
1994年 | 5篇 |
1992年 | 7篇 |
1991年 | 5篇 |
1990年 | 6篇 |
1989年 | 4篇 |
1988年 | 3篇 |
1987年 | 3篇 |
1986年 | 4篇 |
1985年 | 6篇 |
1984年 | 4篇 |
1983年 | 3篇 |
1981年 | 3篇 |
1980年 | 4篇 |
1978年 | 3篇 |
1976年 | 3篇 |
1974年 | 6篇 |
1973年 | 6篇 |
1972年 | 3篇 |
1971年 | 4篇 |
1970年 | 8篇 |
1969年 | 3篇 |
1966年 | 4篇 |
1961年 | 2篇 |
排序方式: 共有531条查询结果,搜索用时 15 毫秒
11.
12.
Miroslava Katsur Zhenhe He Vladimir Vinokur Randolph Corteling Derek M Yellon Sean M Davidson 《Journal of cellular and molecular medicine》2021,25(9):4455-4465
Myocardial infarction requires urgent reperfusion to salvage viable heart tissue. However, reperfusion increases infarct size further by promoting mitochondrial damage in cardiomyocytes. Exosomes from a wide range of different cell sources have been shown to activate cardioprotective pathways in cardiomyocytes, thereby reducing infarct size. Yet, it is currently challenging to obtain highly pure exosomes in quantities enough for clinical studies. To overcome this problem, we used exosomes isolated from CTX0E03 neuronal stem cells, which are genetically stable, conditionally inducible and can be produced on an industrial scale. However, it is unknown whether exosomes from neuronal stem cells may reduce cardiac ischaemia/reperfusion injury. In this study, we demonstrate that exosomes from differentiating CTX0E03 cells can reduce infarct size in mice. In an in vitro assay, these exosomes delayed cardiomyocyte mitochondrial permeability transition pore opening, which is responsible for cardiomyocyte death after reperfusion. The mechanism of MPTP inhibition was via gp130 signalling and the downstream JAK/STAT pathway. Our results support previous findings that exosomes from non-cardiomyocyte-related cells produce exosomes capable of protecting cardiomyocytes from myocardial infarction. We anticipate our findings may encourage scientists to use exosomes obtained from reproducible clinical-grade stocks of cells for their ischaemia/reperfusion studies. 相似文献
13.
David Malinak Rafael Dolezal Vendula Hepnarova Miroslava Hozova Rudolf Andrys Petr Bzonek 《Journal of enzyme inhibition and medicinal chemistry》2013,28(1):478-488
Abstract The series of symmetrical and unsymmetrical isoquinolinium-5-carbaldoximes was designed and prepared for cholinesterase reactivation purposes. The novel compounds were evaluated for intrinsic acetylcholinesterase (AChE) or butyrylcholinesterase (BChE) inhibition, when the majority of novel compounds resulted with high inhibition of both enzymes and only weak inhibitors were selected for reactivation experiments on human AChE or BChE inhibited by sarin, VX, or paraoxon. The AChE reactivation for all used organophosphates was found negligible if compared to the reactivation ability of obidoxime. Importantly, two compounds were found to reactivate BChE inhibited by sarin or VX better to obidoxime at human attainable concentration. One compound resulted as better reactivator of NEMP (VX surrogate)-inhibited BChE than obidoxime. The in vitro results were further rationalized by molecular docking studies showing future directions on designing potent BChE reactivators. 相似文献
14.
Lesia Dmytrenko Michal Cicanic Miroslava Anderova Ivan Vorisek Ole Petter Ottersen Eva Sykova Lydia Vargova 《PloS one》2013,8(7)
Aquaporin-4 (AQP4) is the primary cellular water channel in the brain and is abundantly expressed by astrocytes along the blood-brain barrier and brain-cerebrospinal fluid interfaces. Water transport via AQP4 contributes to the activity-dependent volume changes of the extracellular space (ECS), which affect extracellular solute concentrations and neuronal excitability. AQP4 is anchored by α-syntrophin (α-syn), the deletion of which leads to reduced AQP4 levels in perivascular and subpial membranes. We used the real-time iontophoretic method and/or diffusion-weighted magnetic resonance imaging to clarify the impact of α-syn deletion on astrocyte morphology and changes in extracellular diffusion associated with cell swelling in vitro and in vivo. In mice lacking α-syn, we found higher resting values of the apparent diffusion coefficient of water (ADCW) and the extracellular volume fraction (α). No significant differences in tortuosity (λ) or non-specific uptake (k′), were found between α-syn-negative (α-syn −/−) and α-syn-positive (α-syn +/+) mice. The deletion of α-syn resulted in a significantly smaller relative decrease in α observed during elevated K+ (10 mM) and severe hypotonic stress (−100 mOsmol/l), but not during mild hypotonic stress (−50 mOsmol/l). After the induction of terminal ischemia/anoxia, the final values of ADCW as well as of the ECS volume fraction α indicate milder cell swelling in α-syn −/− in comparison with α-syn +/+ mice. Shortly after terminal ischemia/anoxia induction, the onset of a steep rise in the extracellular potassium concentration and an increase in λ was faster in α-syn −/− mice, but the final values did not differ between α-syn −/− and α-syn +/+ mice. This study reveals that water transport through AQP4 channels enhances and accelerates astrocyte swelling. The substantially altered ECS diffusion parameters will likely affect the movement of neuroactive substances and/or trophic factors, which in turn may modulate the extent of tissue damage and/or drug distribution. 相似文献
15.
Patrick-Denis St-Coeur Mohamed Touaibia Miroslava Cuperlovic-Culf Pier Jr Morin 《基因组蛋白质组与生物信息学报(英文版)》2013,11(4):199-206
Glioblastoma multiforme (GBM) is the most common adult primary tumor of the central nervous system. The current standard of care for glioblastoma patients involves a combination of surgery, radiotherapy and chemotherapy with the alkylating agent temozolomide. Several mechanisms underlying the inherent and acquired temozolomide resistance have been identified and contribute to treatment failure. Early identification of temozolomide-resistant GBM patients and improvement of the therapeutic strategies available to treat this malignancy are of uttermost importance. This review initially looks at the molecular pathways underlying GBM formation and development with a particular emphasis placed on recent therapeutic advances made in the field. Our focus will next be directed toward the molecular mechanisms modulating temozolomide resistance in GBM patients and the strategies envisioned to circumvent this resistance. Finally, we highlight the diagnostic and prognostic value of metabolomics in cancers and assess its potential usefulness in improving the current standard of care for GBM patients. 相似文献
16.
Petra Bonova Jozef BurdaViera Danielisova Miroslava NemethovaMiroslav Gottlieb 《Neurochemistry international》2013
In the clinic delayed post-conditioning would represent an attractive strategy for the survival of vulnerable neurons after an ischemic event. In this paper we studied the impact of ischemia and delayed post-conditioning on blood and brain tissue concentrations of glutamate and protein synthesis. We designed two groups of animals for analysis of brain tissues and blood after global ischemia and post-conditioning, and one for analysis of blood glutamate after transient focal ischemia. 相似文献
17.
Petra Bonova Jozef BurdaViera Danielisova Miroslava NemethovaMiroslav Gottlieb 《Neurochemistry international》2013
The period from stroke initiation to the cessation of penumbra damage spread represents a therapeutic window when expansion can be alleviated. In the present work, we studied some biochemical parameters helpful for the estimation of infarct progression and thus for the application of interventions. 相似文献
18.
19.
20.
Evseeva Nina V. Tkachenko Oksana V. Denisova Alena Yu. Burygin Gennady L. Veselov Dmitry S. Matora Larisa Yu. Shchyogolev Sergei Yu. 《World journal of microbiology & biotechnology》2019,35(12):1-10
World Journal of Microbiology and Biotechnology - Derived from RNA, 5?-ribonucleotides, especially Inosine-5?-monophosphate (IMP) and guanosine-5?-monophosphate (GMP), can enhance... 相似文献