全文获取类型
收费全文 | 3723篇 |
免费 | 271篇 |
国内免费 | 279篇 |
专业分类
4273篇 |
出版年
2024年 | 7篇 |
2023年 | 52篇 |
2022年 | 124篇 |
2021年 | 201篇 |
2020年 | 126篇 |
2019年 | 149篇 |
2018年 | 153篇 |
2017年 | 100篇 |
2016年 | 150篇 |
2015年 | 241篇 |
2014年 | 242篇 |
2013年 | 299篇 |
2012年 | 344篇 |
2011年 | 283篇 |
2010年 | 158篇 |
2009年 | 187篇 |
2008年 | 226篇 |
2007年 | 191篇 |
2006年 | 153篇 |
2005年 | 127篇 |
2004年 | 119篇 |
2003年 | 105篇 |
2002年 | 87篇 |
2001年 | 68篇 |
2000年 | 60篇 |
1999年 | 59篇 |
1998年 | 31篇 |
1997年 | 39篇 |
1996年 | 19篇 |
1995年 | 25篇 |
1994年 | 17篇 |
1993年 | 18篇 |
1992年 | 19篇 |
1991年 | 10篇 |
1990年 | 18篇 |
1989年 | 11篇 |
1988年 | 16篇 |
1987年 | 7篇 |
1986年 | 8篇 |
1985年 | 7篇 |
1984年 | 5篇 |
1983年 | 3篇 |
1982年 | 2篇 |
1981年 | 2篇 |
1979年 | 1篇 |
1974年 | 1篇 |
1969年 | 1篇 |
1949年 | 1篇 |
1948年 | 1篇 |
排序方式: 共有4273条查询结果,搜索用时 0 毫秒
51.
Li Zhibin Hua Zetian Dong Li Zhu Wei He Guangsheng Qu Lijun Qi Na Xu Zhengjin Wang Fang 《Journal of Plant Growth Regulation》2020,39(1):60-71
Journal of Plant Growth Regulation - RAD-seq method is a recently developed, cost-effective, and high-throughput approach for detecting genetic variability based on single-nucleotide polymorphisms... 相似文献
52.
Chaoyi Li Kai Fan Yue Qu Wei Zhai Ai Huang Xiangfu Sun Shijie Xing 《Journal of cellular physiology》2020,235(4):3721-3730
Non-small-cell lung cancer (NSCLC) remains the leading cause of cancer death worldwide. As a platinum-based chemotherapeutic drug, cisplatin has been used for over 30 years in NSCLC treatment while its effects are diminished by drug resistance. Therefore, we aimed to study the potential role of UCA1 in the development of chemoresistance against cisplatin. Real-time polymerase chain reaction, western-blot analysis, and immunofluorescence were used to study the involvement of UCA1, miR-495, and NRF2 in chemoresistance against cisplatin. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was performed to determine the effect of cisplatin on cell proliferation. Computational analysis and luciferase assay were carried out to explore the interaction among UCA1, miR-495, and NRF2. The cisplatin-R group exhibited lower levels of UCA1 and NRF2 expression but a higher level of miR-495 expression than the cisplatin-S group. The growth rate and half-maximal inhibitory concentration of cellular dipeptidyl peptidase (cisplatinum) of the cisplatin-R group were much higher than those in the cisplatin-S group. MiR-495 contained a complementary binding site of UCA1, and the luciferase activity of wild-type UCA1 was significantly reduced after the transfection of miR-495 mimics. MiR-495 directly targeted the 3′-untranslated region (3′-UTR) of NRF2, and the luciferase activity of wild-type NRF2 3′-UTR was evidently inhibited by miR-495 mimics. Finally, UCA1 and NRF2 expressions in the effective group were much lower than that in the ineffective group, along with a much higher level of miR-495 expression. We suggested for the first time that high expression of UCA1 contributed to the development of chemoresistance to cisplatin through the UCA1/miR-495/NRF2 signaling pathway. 相似文献
53.
Liwen Liang Huili Li Ting Cao Lina Qu Lulu Zhang Guo-Chang Fan Peter A. Greer Jianmin Li Douglas L. Jones Tianqing Peng 《The Journal of biological chemistry》2020,295(49):16840
The human cardiovascular system has adapted to function optimally in Earth''s 1G gravity, and microgravity conditions cause myocardial abnormalities, including atrophy and dysfunction. However, the underlying mechanisms linking microgravity and cardiac anomalies are incompletely understood. In this study, we investigated whether and how calpain activation promotes myocardial abnormalities under simulated microgravity conditions. Simulated microgravity was induced by tail suspension in mice with cardiomyocyte-specific deletion of Capns1, which disrupts activity and stability of calpain-1 and calpain-2, and their WT littermates. Tail suspension time-dependently reduced cardiomyocyte size, heart weight, and myocardial function in WT mice, and these changes were accompanied by calpain activation, NADPH oxidase activation, and oxidative stress in heart tissues. The effects of tail suspension were attenuated by deletion of Capns1. Notably, the protective effects of Capns1 deletion were associated with the prevention of phosphorylation of Ser-345 on p47phox and attenuation of ERK1/2 and p38 activation in hearts of tail-suspended mice. Using a rotary cell culture system, we simulated microgravity in cultured neonatal mouse cardiomyocytes and observed decreased total protein/DNA ratio and induced calpain activation, phosphorylation of Ser-345 on p47phox, and activation of ERK1/2 and p38, all of which were prevented by calpain inhibitor-III. Furthermore, inhibition of ERK1/2 or p38 attenuated phosphorylation of Ser-345 on p47phox in cardiomyocytes under simulated microgravity. This study demonstrates for the first time that calpain promotes NADPH oxidase activation and myocardial abnormalities under microgravity by facilitating p47phox phosphorylation via ERK1/2 and p38 pathways. Thus, calpain inhibition may be an effective therapeutic approach to reduce microgravity-induced myocardial abnormalities. 相似文献
54.
55.
56.
Fuxin Zhao Jinyu Wu Anquan Xue Yanfeng Su Xiaojing Wang Xianmin Lu Zhonglou Zhou Jia Qu Xiangtian Zhou 《Human genetics》2013,132(8):913-921
Myopia is a refractive error of the eye that is prevalent worldwide. The most extreme form, high myopia, is usually associated with other ocular disorders such as retinal detachment, macular degeneration, cataract, and glaucoma, and is one of leading causes of blindness. The etiology is complex and has not been fully elucidated. In this study, we identified a novel missense variant of the CCDC111 gene (NM_152683.2: c.265T > G; p.Y89D) in a high myopia family by exome sequencing. The variant was identified in 4 patients from an additional 270 sporadic high myopia patients, but not found in 270 controls. The amino acid is highly conserved across species, and variants giving rise to amino acid substitutions are predicted to be functionally damaging. The CCDC111 gene was ubiquitously expressed in primary cell cultures from human eye tissue, including corneal epithelial cells, choroidal melanoma cells, scleral fibroblasts, retinal epithelial cells, retinal Müller cells, and lens capsule epithelial cells. In summary, our results suggested that the CCDC111 may be a susceptibility gene for high myopia. 相似文献
57.
58.
Chronic obstructive pulmonary disease (COPD) is associated with chronic severe airway inflammation and causes increasing global health problems. New biological markers for COPD prediction and prognosis are urgently necessary. Previous studies indicate that histone deacetylases (HDACs) play essential roles in COPD. This study is to investigate if HDAC2 levels can be used as a promising, easily detected biomarker of COPD. In this paper, 49 COPD patients were enrolled and 42 healthy individuals (smokers or non-smokers) were used as healthy controls. Human bronchial epithelial cells derived from non-smokers, smokers, or COPD patients were grown in primary cultures. Total proteins were harvested from lung tissues or bronchial epithelial cells and then subjected to immunoblot analyses of HDAC2, HDAC3, and HDAC5. Quantitative RT-PCR analysis of HDAC2, HDAC3, and HDAC5 mRNA levels in tissues or cells were also preformed. We found that among the three HDAC proteins, the mRNA and protein levels of HDAC2, but not HDAC3 and HDAC5, in the tissues or cultured cells from patients have a significant correlation with development and prognosis of COPD. These results suggested that HDAC2 levels may serve as a promising, easily detected biomarker of COPD. 相似文献
59.
Yun Xia Wei Qu Li-Na Zhao Hao Han Xue-Feng Yang Xiu-Fa Sun Li-Ping Hao Jian Xu 《Biological trace element research》2013,154(1):103-110
Iodine excess is emerging as a new focus. A better understanding of its hazardous effects on the liver will be of great benefit to health. The aim of this study is to illustrate the effects of iodine excess on hepatic lipid homeostasis and explore its possible mechanisms. One hundred twenty BaLB/c mice were given iodine at different levels (0, 0.3, 0.6, 1.2, 2.4, and 4.8 mg I/L) in drinking water for 1 or 3 months. Lipid parameters and serum thyroid hormones were measured. Hepatic type 1 deiodinase activity and oxidative stress parameters were evaluated. The mRNA expression of sterol regulatory element-binding protein-1c (SREBP-1c) and fatty acid synthase (FAS) was detected by real-time polymerase chain reaction. Dose-dependent increase of hepatic triglyceride content was detected (r?=?0.680, P?<?0.01) in iodine-loaded groups. Evident hepatic steatosis was observed in 2.4 and 4.8 mg I/L iodine-loaded groups. The activities of antioxidant enzymes (glutathione peroxidase and superoxide dismutase) were decreased, and the malondialdehyde level was increased by excessive iodine in both serum and liver in a dose-dependent manner, accompanying the decrease of hepatic D1 activity. That resulted in the increase of serum total thyroxine and the decrease of serum total triiodothyronine in iodine-loaded groups. The mRNA expression of SREBP-1c and FAS was increased in iodine-loaded groups in response to the change of serum triiodothyronine. Present findings demonstrated that iodine excess could dose dependently induce hepatic steatosis. Furthermore, our data suggested that the disturbance of thyroid hormone metabolism involving oxidative stress may play a critical role in iodine excess-induced hepatic steatosis. 相似文献