全文获取类型
收费全文 | 4921篇 |
免费 | 301篇 |
国内免费 | 2篇 |
专业分类
5224篇 |
出版年
2024年 | 8篇 |
2023年 | 16篇 |
2022年 | 71篇 |
2021年 | 80篇 |
2020年 | 52篇 |
2019年 | 71篇 |
2018年 | 100篇 |
2017年 | 86篇 |
2016年 | 156篇 |
2015年 | 263篇 |
2014年 | 318篇 |
2013年 | 334篇 |
2012年 | 484篇 |
2011年 | 424篇 |
2010年 | 269篇 |
2009年 | 240篇 |
2008年 | 336篇 |
2007年 | 263篇 |
2006年 | 257篇 |
2005年 | 220篇 |
2004年 | 190篇 |
2003年 | 169篇 |
2002年 | 148篇 |
2001年 | 127篇 |
2000年 | 124篇 |
1999年 | 112篇 |
1998年 | 39篇 |
1997年 | 28篇 |
1996年 | 20篇 |
1995年 | 21篇 |
1994年 | 20篇 |
1993年 | 17篇 |
1992年 | 26篇 |
1991年 | 23篇 |
1990年 | 14篇 |
1989年 | 11篇 |
1988年 | 8篇 |
1987年 | 4篇 |
1986年 | 9篇 |
1984年 | 4篇 |
1982年 | 4篇 |
1981年 | 3篇 |
1977年 | 4篇 |
1976年 | 4篇 |
1974年 | 7篇 |
1973年 | 3篇 |
1972年 | 3篇 |
1969年 | 4篇 |
1967年 | 5篇 |
1966年 | 5篇 |
排序方式: 共有5224条查询结果,搜索用时 15 毫秒
111.
Backgroud A newly acquired rhesus macaque was suffering from rapid destruction of the left cheek caused by necrotizing stomatitis. Methods To restore reconstructive surgery and intensive care with antibiotics, wound protection, wound healing agents, and debridement were applied. Results Staphylococcus aureus and Enterococcus faecalis were isolated from the culture of the lesion, and the antibiotic susceptibility test revealed methicillin‐resistant Staphylococcus aureus infection. Vancomycin and ampicillin‐sulbactam effectively treated the bacterial infections, and reconstructive surgery was performed once the infection was cleared. Topical application of recombinant human epidermal growth factor (rhEGF) was useful to treat exposed wound of the noma lesion. Conclusions Simian noma associated with methicillin‐resistant Staphylococcus aureus (MRSA) had not previously been reported in non‐human primates. Although noma associated with MRSA is hard to cure because of its rapid and destructive progress, the aggressive therapy used in this study led to the successful resolution of an acute necrotic stomatitis lesion in a rhesus macaque. 相似文献
112.
113.
Soucy KG Lim HK Kim JH Oh Y Attarzadeh DO Sevinc B Kuo MM Shoukas AA Vazquez ME Berkowitz DE 《Radiation research》2011,176(4):474-485
Ionizing radiation has been implicated in the development of significant cardiovascular complications. Since radiation exposure is associated with space exploration, astronauts are potentially at increased risk of accelerated cardiovascular disease. This study investigated the effect of high atomic number, high-energy (HZE) iron-ion radiation on vascular and endothelial function as a model of space radiation. Rats were exposed to a single whole-body dose of iron-ion radiation at doses of 0, 0.5 or 1 Gy. In vivo aortic stiffness and ex vivo aortic tension responses were measured 6 and 8 months after exposure as indicators of chronic vascular injury. Rats exposed to 1 Gy iron ions demonstrated significantly increased aortic stiffness, as measured by pulse wave velocity. Aortic rings from irradiated rats exhibited impaired endothelial-dependent relaxation consistent with endothelial dysfunction. Acute xanthine oxidase (XO) inhibition or reactive oxygen species (ROS) scavenging restored endothelial-dependent responses to normal. In addition, XO activity was significantly elevated in rat aorta 4 months after whole-body irradiation. Furthermore, XO inhibition, initiated immediately after radiation exposure and continued until euthanasia, completely inhibited radiation-dependent XO activation. ROS production was elevated after 1 Gy irradiation while production of nitric oxide (NO) was significantly impaired. XO inhibition restored NO and ROS production. Finally, dietary XO inhibition preserved normal endothelial function and vascular stiffness after radiation exposure. These results demonstrate that radiation induced XO-dependent ROS production and nitroso-redox imbalance, leading to chronic vascular dysfunction. As a result, XO is a potential target for radioprotection. Enhancing the understanding of vascular radiation injury could lead to the development of effective methods to ameliorate radiation-induced vascular damage. 相似文献
114.
Kim JY Oh MH Bernard LP Macara IG Zhang H 《The Journal of biological chemistry》2011,286(43):37615-37624
Dendritic spines are actin-rich structures, the formation and plasticity of which are regulated by the Rho GTPases in response to synaptic input. Although several guanine nucleotide exchange factors (GEFs) have been implicated in spine development and plasticity in hippocampal neurons, it is not known how many different Rho GEFs contribute to spine morphogenesis or how they coordinate the initiation, establishment, and maintenance of spines. In this study, we screened 70 rat Rho GEFs in cultured hippocampal neurons by RNA interference and identified a number of candidates that affected spine morphogenesis. Of these, Dock180, which plays a pivotal role in a variety of cellular processes including cell migration and phagocytosis, was further investigated. We show that depletion of Dock180 inhibits spine morphogenesis, whereas overexpression of Dock180 promotes spine morphogenesis. ELMO1, a protein necessary for in vivo functions of Dock180, functions in a complex with Dock180 in spine morphogenesis through activating the Rac GTPase. Moreover, RhoG, which functions upstream of the ELMO1/Dock180 complex, is also important for spine formation. Together, our findings uncover a role for the RhoG/ELMO1/Dock180 signaling module in spine morphogenesis in hippocampal neurons. 相似文献
115.
Ooi CH Oh HK Wang HZ Tan AL Wu J Lee M Rha SY Chung HC Virshup DM Tan P 《PLoS genetics》2011,7(12):e1002415
MicroRNAs (miRNAs) are important components of cellular signaling pathways, acting either as pathway regulators or pathway targets. Currently, only a limited number of miRNAs have been functionally linked to specific signaling pathways. Here, we explored if gene expression signatures could be used to represent miRNA activities and integrated with genomic signatures of oncogenic pathway activity to identify connections between miRNAs and oncogenic pathways on a high-throughput, genome-wide scale. Mapping >300 gene expression signatures to >700 primary tumor profiles, we constructed a genome-wide miRNA-pathway network predicting the associations of 276 human miRNAs to 26 oncogenic pathways. The miRNA-pathway network confirmed a host of previously reported miRNA/pathway associations and uncovered several novel associations that were subsequently experimentally validated. Globally, the miRNA-pathway network demonstrates a small-world, but not scale-free, organization characterized by multiple distinct, tightly knit modules each exhibiting a high density of connections. However, unlike genetic or metabolic networks typified by only a few highly connected nodes ("hubs"), most nodes in the miRNA-pathway network are highly connected. Sequence-based computational analysis confirmed that highly-interconnected miRNAs are likely to be regulated by common pathways to target similar sets of downstream genes, suggesting a pervasive and high level of functional redundancy among coexpressed miRNAs. We conclude that gene expression signatures can be used as surrogates of miRNA activity. Our strategy facilitates the task of discovering novel miRNA-pathway connections, since gene expression data for multiple normal and disease conditions are abundantly available. 相似文献
116.
Lee SW Won JY Lee HY Lee HJ Youn SW Lee JY Cho CH Cho HJ Oh S Chae IH Kim HS 《Molecular medicine (Cambridge, Mass.)》2011,17(9-10):1095-1106
Early reperfusion after myocardial ischemia that is essential for tissue salvage also causes myocardial and vascular injury. Cardioprotection during reperfusion therapy is an essential aspect of treating myocardial infarction. Angiopoietin-1 is an endothelial-specific angiogenic factor. The potential effects of angiopoietin-1 on cardiomyocytes and vascular cells undergoing reperfusion have not been investigated. We propose a protective mechanism whereby angiopoietin-1 increases the integrity of the endothelial lining and exerts a direct survival effect on cardiomyocytes under myocardial ischemia followed by reperfusion. First, we found that angiopoietin-1 prevents vascular leakage through regulating vascular endothelial (VE)-cadherin phosphorylation. The membrane expression of VE-cadherin was markedly decreased on hypoxia/reoxygenation but was restored by angiopoietin-1 treatment. Interestingly, these effects were mediated by the facilitated binding between SH2 domain-containing tyrosine phosphatase (SHP2) or receptor protein tyrosine phosphatase μ (PTPμ) and VE-cadherin, leading to dephosphorylation of VE-cadherin. siRNA against SHP2 or PTPμ abolished the effect of angiopoietin-1 on VE-cadherin dephosphorylation and thereby decreased levels of membrane-localized VE-cadherin. Second, we found that angiopoietin-1 prevented cardiomyocyte death, although cardiomyocytes lack the angiopoietin-1 receptor Tie2. Angiopoietin-1 increased cardiomyocyte survival through integrin-β1-mediated extracellular signal-regulated kinase (ERK) phosphorylation, which inhibited caspase-9 through phosphorylation at Thr12? and subsequently reduced active caspase-3. Neutralizing antibody against integrin-β1 blocked these protective effects. In a mouse myocardial ischemia/reperfusion model, angiopoietin-1 enhanced cardiac function and reduction in left ventricular-end systolic dimension (LV-ESD) and left ventricular-end diastolic dimension (LV-EDD) with an increase in ejection fraction (EF) and fractional shortening (FS). Our findings suggest the novel cardioprotective mechanisms of angiopoietin-1 that are achieved by reducing both vascular leakage and cardiomyocyte death after ischemia/reperfusion injury. 相似文献
117.
Tae-Hun Kim Eun-Joo Yang Kyung-Chul Shin Kyeong-Hwan Hwang Jun Seong Park Deok-Kun Oh 《Biotechnology and Bioprocess Engineering》2018,23(2):183-193
Ginsenoside compound K is an essential ingredient in nutritional supplements, cosmetics, and traditional medicines. However, cultivation for the production of enzymes involved in ginsenoside biotransformation has not been attempted in a fermenter. The host strain Escherichia coli ER2566 and the constitutive pHCE vector were selected for the efficient production of β-D-glycosidase, and expression medium composition to produce Sulfolobus solfataricus β-glycosidase expressed in E. coli was optimized in flask and batch cultures. The total activity of β-Dglycosidase in fed-batch culture using a fermenter increased 14-fold before optimization. S. solfataricus β-D-glycosidase and Thermotoga petrophila α-L-arabinofuranosidase were produced in a fed-batch culture. These two enzymes completely converted protopanaxadiol-type ginsenosides in ginseng leaf extract obtained from discarded ginseng leaves as a renewable substrate to compound K. The effective bioprocess for compound K production developed here will contribute to the industrial biological production of compound K. 相似文献
118.
119.
Among the various Ni‐based layered oxide systems in the form of LiNi1‐y‐zCoyAlzO2 (NCA), the compostions between y = 0.1–0.15, z = 0.05 are the most successful and commercialized cathodes used in electric vehicles (EVs) and hybrid electric vehicles (HEVs). However, tremendous research effort has been dedicted to searching for better composition in NCA systems to overcome the limitations of these cathodes, particularly those that arise when they are used use at high discharge/charge rates (>5C) and in high temperature (60 °C) environments. In addition, improving the thermal stability at 4.5 V is also very important in terms of the total amount of heat generated and the onset temperature. Here, a new NCA composition in the form of LiNi0.81Co0.1Al0.09O2 (y = 0.1, z = 0.09) is reported for the first time. Compared to the LiNi0.85Co0.1Al0.05O2 cathode, LiNi0.81Co0.1Al0.09O2 exhibits an excellent rate capability of 155 mAh g?1 at 10 C with a cut‐off voltage range between 3 and 4.5 V, corresponding to 562 Wh kg?1 at 24 °C. It additionally provides significantly improved thermal stability and electrochemical performance at the high temperature of 60 °C, with a discharge capacity of 122 mAh g?1 after 200 cycles with capacity retention of 59%. 相似文献
120.
Emmanuel Margolin Youngjun J. Oh Matthew Verbeek Jason Naude Daniel Ponndorf Yulia Alexandrovna Meshcheriakova Hadrien Peyret Michiel T. van Diepen Ros Chapman Ann E. Meyers George Peter Lomonossoff Nobuyuki Matoba Anna‐Lise Williamson Edward P. Rybicki 《Plant biotechnology journal》2020,18(10):2109-2117