全文获取类型
收费全文 | 3997篇 |
免费 | 346篇 |
国内免费 | 358篇 |
出版年
2024年 | 6篇 |
2023年 | 50篇 |
2022年 | 106篇 |
2021年 | 217篇 |
2020年 | 141篇 |
2019年 | 175篇 |
2018年 | 163篇 |
2017年 | 126篇 |
2016年 | 200篇 |
2015年 | 234篇 |
2014年 | 258篇 |
2013年 | 299篇 |
2012年 | 347篇 |
2011年 | 316篇 |
2010年 | 194篇 |
2009年 | 178篇 |
2008年 | 217篇 |
2007年 | 160篇 |
2006年 | 178篇 |
2005年 | 149篇 |
2004年 | 145篇 |
2003年 | 110篇 |
2002年 | 119篇 |
2001年 | 97篇 |
2000年 | 85篇 |
1999年 | 80篇 |
1998年 | 47篇 |
1997年 | 44篇 |
1996年 | 39篇 |
1995年 | 37篇 |
1994年 | 29篇 |
1993年 | 21篇 |
1992年 | 21篇 |
1991年 | 25篇 |
1990年 | 13篇 |
1989年 | 6篇 |
1988年 | 10篇 |
1987年 | 16篇 |
1986年 | 8篇 |
1985年 | 8篇 |
1984年 | 8篇 |
1983年 | 4篇 |
1982年 | 2篇 |
1981年 | 5篇 |
1980年 | 1篇 |
1979年 | 2篇 |
1978年 | 2篇 |
1977年 | 1篇 |
1974年 | 1篇 |
1971年 | 1篇 |
排序方式: 共有4701条查询结果,搜索用时 46 毫秒
91.
Yuki Ito Jose Luis Vela Fumiko Matsumura Hitomi Hoshino Aaron Tyznik Heeseob Lee Enrico Girardi Dirk M. Zajonc Robert Liddington Motohiro Kobayashi Xingfeng Bao Jeanna Bugaytsova Thomas Borén Rongsheng Jin Yinong Zong Peter H. Seeberger Jun Nakayama Mitchell Kronenberg Minoru Fukuda 《PloS one》2013,8(12)
Approximately 10–15% of individuals infected with Helicobacter pylori will develop ulcer disease (gastric or duodenal ulcer), while most people infected with H. pylori will be asymptomatic. The majority of infected individuals remain asymptomatic partly due to the inhibition of synthesis of cholesteryl α-glucosides in H. pylori cell wall by α1,4-GlcNAc-capped mucin O-glycans, which are expressed in the deeper portion of gastric mucosa. However, it has not been determined how cholesteryl α-glucosyltransferase (αCgT), which forms cholesteryl α-glucosides, functions in the pathogenesis of H. pylori infection. Here, we show that the activity of αCgT from H. pylori clinical isolates is highly correlated with the degree of gastric atrophy. We investigated the role of cholesteryl α-glucosides in various aspects of the immune response. Phagocytosis and activation of dendritic cells were observed at similar degrees in the presence of wild-type H. pylori or variants harboring mutant forms of αCgT showing a range of enzymatic activity. However, cholesteryl α-glucosides were recognized by invariant natural killer T (iNKT) cells, eliciting an immune response in vitro and in vivo. Following inoculation of H. pylori harboring highly active αCgT into iNKT cell-deficient (Jα18−/−) or wild-type mice, bacterial recovery significantly increased in Jα18−/− compared to wild-type mice. Moreover, cytokine production characteristic of Th1 and Th2 cells dramatically decreased in Jα18−/− compared to wild-type mice. These findings demonstrate that cholesteryl α-glucosides play critical roles in H. pylori-mediated gastric inflammation and precancerous atrophic gastritis. 相似文献
92.
Guo Wenfang Li Gangqiang Wang Nan Yang Caifeng Zhao Yanan Peng Huakang Liu Dehu Chen Sanfeng 《Plant molecular biology》2020,102(4-5):553-567
Plant Molecular Biology - Overexpression of K2-NhaD in transgenic cotton resulted in phenotypes with strong salinity and drought tolerance in greenhouse and field experiments, increased expression... 相似文献
93.
Wang Pei Wang Chun-Mei Gao Li Cui Yan-Nong Yang Hai-Li de Silva Nayana D. G. Ma Qing Bao Ai-Ke Flowers Timothy J. Rowland Owen Wang Suo-Min 《Plant and Soil》2020,448(1-2):603-620
Plant and Soil - Uncontrolled uptake of Na+ is the reason that many species are sensitive to salinity. Suberin is a protective barrier found in the walls of root endodermal cells that appears to be... 相似文献
94.
Ju Wen Sun Tiantian Lu Wenyi Smith Alhaji Osman Bao Yurong Adzraku Seyram Yao Qi Kunming Xu Kailin Qiao Jianlin Zeng Lingyu 《Molecular biology reports》2020,47(4):2735-2748
Molecular Biology Reports - Murine bone marrow-derived macrophages (M0) and M1- and M2-polarized macrophages are being widely used as a laboratory model for polarized macrophages related molecular... 相似文献
95.
Ding Anqi Bao Fei Zhang Tengxun Yang Weiru Wang Jia Cheng Tangren Zhang Qixiang 《Molecular biology reports》2020,47(9):6635-6647
Molecular Biology Reports - Prunus sibirica and Prunus mume are closely related plant species that differ in cold tolerance. Hybrids of P. sibirica and true mume, belonging to the apricot mei... 相似文献
96.
Chen Jiajia Yang Saishuai Wu Chunshuai Cui Zhiming Wan Yangyang Xu Guanhua Bao Guofeng Zhang Jinlong Chen Chu Song Dianwen 《Neurochemical research》2020,45(10):2302-2311
Neurochemical Research - Spinal cord injury (SCI) is one of the diseases with high probability of causing disability in human beings, and there is no reliable treatment at present. Neuronal... 相似文献
97.
Jia Wang Qiujing Zhang Qingqing Zhu Chengxiang Liu Xueli Nan Fuxia Wang Lihua Fang Jie Liu Chao Xie Shuai Fu Bao Song 《Journal of cellular physiology》2020,235(2):1296-1308
With the participation of the existing treatment methods, the prognosis of advanced clear-cell renal cell carcinoma (ccRCC) is poor. More evidence indicates the presence of methylation in ccRCC cancer cells, but there is a lack of studies on methylation-driven genes in ccRCC. We analyzed the open data of ccRCC in The Cancer Genome Atlas database to obtain ccRCC-related methylation-driven genes, and then carried out pathway enrichment, survival, and joint survival analyses. More important, we deeply explored the correlation between differential methylation sites and the expression of these driving genes. Finally, we screened 29 methylation-driven genes via MethylMix, of which six were significantly associated with the survival of ccRCC patients. This study demonstrated that the effect of hypermethylation or hypomethylation on prognosis is different, and the level of methylation of key methylation sites is associated with gene expression. We identified methylation-driven genes independently predicting prognosis in ccRCC, which offers theoretical support in bioinformatics for the study of methylation in ccRCC and a new perspective for the epigenetic study of ccRCC. 相似文献
98.
Yanglin Chen Baojiang Wu Li Zheng Caixia Wu Mengyi Wei Chen Chen Xihe Li Siqin Bao 《Journal of cellular physiology》2020,235(11):8640-8652
We recently reported that epiblast stem cells (EpiSCs)-like cells could be derived from preimplantation embryos (named as AFSCs). Here, we established AFSCs from pre-implantation embryos of multiple mouse strains and showed that unlike EpiSCs, the derivation efficiency of AFSCs was affected by the genetic background. We then used AFSCs lines to dissect the roles of Activin A (Act A) and basic fibroblast growth factor and reported that Act A alone was capable of maintaining self-renewal but not developmental potential in vivo. Finally, we established a novel experimental system, in which AFSCs were efficiently converted to multipotent progenitor stem cells using Act A and bone morphogenetic protein 4 (named as ABSCs). Importantly, these ABSCs contributed to neural mesodermal progenitors and lateral plate mesoderm in postimplantation chimeras. Taken together, our study established a robust experimental system for the generation of specific multipotent progenitor stem cells that was self-renewable and capable of contributing to embryonic and extra-embryonic tissues. 相似文献
99.
Zhong Chen Lahcen Jaafar Davies G. Agyekum Haiyan Xiao Marlene F. Wade R. Ileng Kumaran David L. Spector Gang Bao Matthew H. Porteus William S. Dynan Steffen E. Meiler 《Nucleic acids research》2013,41(19):e182
Engineered nucleases, which incise the genome at predetermined sites, have a number of laboratory and clinical applications. There is, however, a need for better methods for controlled intracellular delivery of nucleases. Here, we demonstrate a method for ligand-mediated delivery of zinc finger nucleases (ZFN) proteins using transferrin receptor-mediated endocytosis. Uptake is rapid and efficient in established mammalian cell lines and in primary cells, including mouse and human hematopoietic stem-progenitor cell populations. In contrast to cDNA expression, ZFN protein levels decline rapidly following internalization, affording better temporal control of nuclease activity. We show that transferrin-mediated ZFN uptake leads to site-specific in situ cleavage of the target locus. Additionally, despite the much shorter duration of ZFN activity, the efficiency of gene correction approaches that seen with cDNA-mediated expression. The approach is flexible and general, with the potential for extension to other targeting ligands and nuclease architectures. 相似文献
100.
A targeted approach for direct topical antimicrobial delivery involving the formulation of impregnated freeze-dried wafers prepared from a natural polymer has been assessed to consider potential for treatment of wounded skin. The synthetic cationic antimicrobial peptides (CAPs) NP101 and NP108 were found to have modest in vitro activity against bacterial species commonly associated with wound infections. Minimum inhibitory concentration/minimum bactericidal concentrations against Escherichia coli, Staphylococcus aureus and Pseudomonas aeruginosa were found to be 0.31 mg/ml for NP101 and 0.25–0.5 mg/ml for NP108. Rapid, substantial cytoplasmic potassium loss was induced by NP108 in E. coli, but not the other species. Through scanning electron microscopy, both CAPs were observed to alter cell morphology, prevent normal septation, promote cell aggregation and trigger release or formation of extracellular filaments. Wafers harbouring these agents displayed substantial antibacterial activity when assessed by standard diffusion assay. These data confirm that topical delivery of CAPs, through their incorporation within freeze-dried wafer formulations prepared from natural polymers, represents a potential viable approach for treating skin infection. 相似文献