全文获取类型
收费全文 | 4947篇 |
免费 | 385篇 |
国内免费 | 268篇 |
专业分类
5600篇 |
出版年
2024年 | 9篇 |
2023年 | 60篇 |
2022年 | 141篇 |
2021年 | 233篇 |
2020年 | 160篇 |
2019年 | 191篇 |
2018年 | 186篇 |
2017年 | 115篇 |
2016年 | 215篇 |
2015年 | 308篇 |
2014年 | 329篇 |
2013年 | 352篇 |
2012年 | 430篇 |
2011年 | 406篇 |
2010年 | 239篇 |
2009年 | 229篇 |
2008年 | 274篇 |
2007年 | 247篇 |
2006年 | 201篇 |
2005年 | 159篇 |
2004年 | 150篇 |
2003年 | 149篇 |
2002年 | 117篇 |
2001年 | 90篇 |
2000年 | 84篇 |
1999年 | 65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 | 10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5600条查询结果,搜索用时 15 毫秒
941.
942.
Zhao-Yang Li Pu-Liu Zhao-Hong Chen Feng-Hui An Li-Hua Li Li-Li Chang-Yan Guo Yan Gu Zhe Liu Tie-Bing Zhu Lian-Sheng Wang Chun-Jian Li Xiang-Qing Kong Wen-Zhu Ma Zhi-Jian Yang En-Zhi Jia 《PloS one》2014,9(10)
Objective
to explore the impact of admission serum creatinine concentration on the in-hospital mortality and its interaction with age and gender in patients with acute ST-segment elevation myocardial infarction (STEMI) in China.Methods
1424 acute STEMI patients were enrolled in the study. Anthropometric and laboratory measurements were collected from every patient. A Cox proportional hazards regression model was used to determine the relationships between the admission serum creatinine level (Cr level), age, sex and the in-hospital mortality. A crossover analysis and a stratified analysis were used to determine the combined impact of Cr levels with age and gender.Results
Female (HR 1.687, 95%CI 1.051∼2.708), elevated Cr level (HR 5.922, 95%CI 3.780∼9,279) and old age (1.692, 95%CI 1.402∼2.403) were associated with a high risk of death respectively. After adjusting for other confounders, the renal dysfunction was still independently associated with a higher risk of death (HR 2.48, 95% CI 1.32∼4.63), while female gender (HR 1.19, 95%CI 0.62∼2.29) and old age (HR 1.77, 95%CI 0.92∼3.37) was not. In addition, crossover analysis revealed synergistic effects between elevated Cr level and female gender (SI = 3.01, SIM = 2.10, AP = 0.55). Stratified analysis showed that the impact of renal dysfunction on in-hospital mortality was more pronounced in patients <60 years old (odds ratios 11.10, 95% CI 3.72 to 33.14) compared with patients 60 to 74 years old (odds ratios 5.18, 95% CI 2.48∼10.83) and patients ≥75years old (odds ratios 3.99, 95% CI 1.89 to 8.42).Conclusion
Serum Cr concentration on admission was a strong predictor for in-hospital mortality among Chinese acute STEMI patients especially in the young and the female. 相似文献943.
944.
Jinkyung Cho Inhwan Lee Donghyun Kim Yeojung Koh Jiyoung Kong Sanghee Lee Hyunsik Kang 《Journal of Exercise Nutrition & Biochemistry》2014,18(4):339-346
[Purpose]
The aim of this study was to investigate the effects of aerobic exercise training on a high fat diet (HFD)-induced fatty liver and its metabolic complications in C57BL/6 mice.[Methods]
Mice at 5-month old (n = 30) were randomly assigned to standard chow (SC + CON, n = 10) and high-fat diet (HFD, n = 20), and they were subjected to SC and HFD, respectively, for 23-week. After 15-week of HFD, mice in the HFD group were further assigned to HFD (HFD + CON, n = 10) or exercise training (HFD + EX, n = 10) groups. The HFD + EX mice were subjected to aerobic treadmill running during the last 8-week of the 23-week HFD course. Outcomes included hepatic steatosis, insulin resistance, and expression of genes involved in mitochondrial function and/or fatty oxidation as well as de novo lipogenesis and/or triacylglycerol (TAG) synthesis.[Results]
Treadmill running ameliorated impaired glucose tolerance and insulin resistance secondary to the HFD. The beneficial effects of treadmill running were associated with enhanced molecular markers of mitochondrial function and/or fatty acids oxidation (i.e., PPARα and CPT1a mRNAs, pAMPK/AMPK, pACC, and SIRT1 protein) as well as suppressed expression of de novo lipogenesis and/or TAG synthesis (i.e., SREBP1c, lipin1 and FAS mRNAs) in the liver.[Conclusion]
The current findings suggest that aerobic exercise training is an effective and non-pharmacological means to combat fatty liver and its metabolic complications in HFD-induced obese mice. 相似文献945.
Yuan Liu Cuifu Yu Zhenlong Shao Xiaohong Xia Tumei Hu Weiyao Kong Xiaoyue He Wenshuang Sun Yuanfei Deng Yuning Liao Hongbiao Huang 《Cell death & disease》2021,12(10)
Androgen receptor splice variant 7 (AR-V7), a form of ligand-independent and constitutively activating variant of androgen receptor (AR), is considered as the key driver to initiate castration-resistant prostate cancer (CRPC). Because AR-V7 lacks ligand-binding domain, the AR-targeted therapies that aim to inactivate AR signaling through disrupting the interaction between AR and androgen are limited in CRPC. Thus, the emergence of AR-V7 has become the greatest challenge for treating CRPC. Targeting protein degradation is a recently proposed novel avenue for cancer treatment. Our previous studies have been shown that the oncoprotein AR-V7 is a substrate of the proteasome. Identifying novel drugs that can trigger the degradation of AR-V7 is therefore critical to cure CRPC. Here we show that nobiletin, a polymethoxylated flavonoid derived from the peel of Citrus fruits, exerts a potent anticancer activity via inducing G0/G1 phase arrest and enhancing the sensitivity of cells to enzalutamide in AR-V7 positive PC cells. Mechanically, we unravel that nobiletin selectively induces proteasomal degradation of AR-V7 (but not AR). This effect relies on its selective inhibition of the interactions between AR-V7 and two deubiquitinases USP14 and USP22. These findings not only enrich our understanding on the mechanism of AR-V7 degradation, but also provide an efficient and druggable target for overcoming CRPC through interfering the stability of AR-V7 mediated by the interaction between AR-V7 and deubiquitinase.Subject terms: Drug development, Translational research 相似文献
946.
947.
Daxiang Cui Cengiz S. Ozkan Sathyajith Ravindran Yong Kong Huajian Gao 《Molecular & cellular biomechanics : MCB》2004,1(2):113-122
Experiments on encapsulating Pt--labelled DNA molecules inside multiwalled carbon nanotubes (MWCNT) were performed under temperature and pressure conditions of 400K and 3 Bar. The DNA-CNT hybrids were purified via agarose gel electrophoresis and analyzed via high resolution transmission electron microscopy (HR-TEM) and energy dispersive X-ray spectroscopy (EDX). The results showed that the Pt-labelled DNA molecules attached to the outside walls of CNTs could be removed by electrophoresis. The HR-TEM and EDX results demonstrated that 2-3% of the Pt-labelled DNA molecules were successfully encapsulated inside the MWCNTs. The experimental study complements our previous molecular dynamics simulations on encapsulation of single stranded DNA oligonucleotides inside single wall carbon nanotubes under similar conditions in water. The van der Waals interaction between CNT and Pt-labelled DNA is believed to be the main driving force for this phenomenon. The DNA-CNT molecular complex could be further explored for potential applications in bio-nanotechnology. 相似文献
948.
949.
Directed evolution of operon of trehalose-6-phosphate synthase/phosphatase from Escherichia coli 总被引:1,自引:0,他引:1
Kong X Liu Y Gou X Zhang H Wang X Zhang J 《Biochemical and biophysical research communications》2001,280(1):396-400
Trehalose is a nonspecific protective agent for biomacromolecules. Trehalose-6-phosphate synthase (OtsA)/phosphatase (OtsB), which is encoded by the gene operon otsBA located at -42 of the Escherichia coli genome, is the main enzyme system that catalyzes the synthesis of trehalose in E. coli. We cloned the operon and modified it by directed evolution. Unlike in the previously reported work, we modified the whole operon and screened the positive mutant simultaneously. Thus we believe that the gene complex solves the negative effects between two enzymes if one of them diversifies its structure or functions and finds the form most suitable for trehalose synthesis. It thus mimics the natural process, in which the functional improvement of organisms is related to alterations in coordinated enzymes. The evolution procedure was carried out in a sequence of error-prone PCR, shuffling PCR, and then strict screening of the mutants. After screening of a library of more than 4000 colonies, about 15 positive colonies were analyzed, resulting in a higher concentration of trehalose than control. One of them, E. coli TS7, shows 12.3-fold higher trehalose synthesis ability than E. coli DH5alpha. In contrast, we introduced the cDNA sequence of the tps1 gene from Saccharomyces cerevisiae, which has 54% identity with the gene otsA, as one of the templates in shuffling PCR. By hybrid evolution and screening, we obtained 10 positive colonies with higher concentrations of trehalose than control. E. coli TS22 appears to have 5.3-fold higher trehalose synthesis ability than E. coli DH5alpha and 1.6-fold more than E. coli DEF3(pOTS11). This result demonstrated that coevolution and hybrid evolution, as powerful protocols in protein engineering, are effective in modifying enzyme. It indicates that repeating the process of genomic evolution in nature is feasible. 相似文献
950.
Y Li Y Kong Z Zhou H Chen Z Wang Y-C Hsieh D Zhao X Zhi J Huang J Zhang H Li C Chen 《Cell death & disease》2013,4(11):e935
Apoptosis resistance is a hurdle for cancer treatment. HECTD3, a new E3 ubiquitin ligase, interacts with caspase-8 death effector domains and ubiquitinates caspase-8 with K63-linked polyubiquitin chains that do not target caspase-8 for degradation but decrease the caspase-8 activation. HECTD3 depletion can sensitize cancer cells to extrinsic apoptotic stimuli. In addition, HECTD3 inhibits TNF-related apoptosis-inducing ligand (TRAIL)-induced caspase-8 cleavage in an E3 ligase activity-dependent manner. Mutation of the caspase-8 ubiquitination site at K215 abolishes the HECTD3 protection from TRAIL-induced cleavage. Finally, HECTD3 is frequently overexpressed in breast carcinomas. These findings suggest that caspase-8 ubiquitination by HECTD3 confers cancer cell survival. 相似文献