全文获取类型
收费全文 | 61655篇 |
免费 | 18129篇 |
国内免费 | 3902篇 |
出版年
2024年 | 117篇 |
2023年 | 550篇 |
2022年 | 1382篇 |
2021年 | 2476篇 |
2020年 | 3515篇 |
2019年 | 5280篇 |
2018年 | 5278篇 |
2017年 | 5186篇 |
2016年 | 5570篇 |
2015年 | 6156篇 |
2014年 | 6280篇 |
2013年 | 6871篇 |
2012年 | 5158篇 |
2011年 | 4472篇 |
2010年 | 4847篇 |
2009年 | 3392篇 |
2008年 | 2541篇 |
2007年 | 1922篇 |
2006年 | 1673篇 |
2005年 | 1577篇 |
2004年 | 1431篇 |
2003年 | 1340篇 |
2002年 | 1179篇 |
2001年 | 994篇 |
2000年 | 821篇 |
1999年 | 699篇 |
1998年 | 380篇 |
1997年 | 347篇 |
1996年 | 329篇 |
1995年 | 307篇 |
1994年 | 267篇 |
1993年 | 184篇 |
1992年 | 237篇 |
1991年 | 165篇 |
1990年 | 151篇 |
1989年 | 133篇 |
1988年 | 86篇 |
1987年 | 104篇 |
1986年 | 63篇 |
1985年 | 67篇 |
1984年 | 46篇 |
1983年 | 34篇 |
1982年 | 37篇 |
1981年 | 21篇 |
1980年 | 10篇 |
1979年 | 6篇 |
1889年 | 1篇 |
1882年 | 1篇 |
1881年 | 1篇 |
1873年 | 1篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
111.
112.
Xin Deng Guoli Zhang Ling Zhang Yan Feng Zehong Li GuangMou Wu Yuhuan Yue Gensong Li Yu Cao Ping Zhu 《PloS one》2015,10(11)
Non-viral gene delivery system with many advantages has a great potential for the future of gene therapy. One inherent obstacle of such approach is the uptake by endocytosis into vesicular compartments. Receptor-mediated gene delivery method holds promise to overcome this obstacle. In this study, we developed a receptor-mediated gene delivery system based on a combination of the Pseudomonas exotoxin A (PE), which has a receptor binding and membrane translocation domain, and the hyperthermophilic archaeal histone (HPhA), which has the DNA binding ability. First, we constructed and expressed the rPE-HPhA fusion protein. We then examined the cytotoxicity and the DNA binding ability of rPE-HPhA. We further assessed the efficiency of transfection of the pEGF-C1 plasmid DNA to CHO cells by the rPE-HPhA system, in comparison to the cationic liposome method. The results showed that the transfection efficiency of rPE-HPhA was higher than that of cationic liposomes. In addition, the rPE-HPhA gene delivery system is non-specific to DNA sequence, topology or targeted cell type. Thus, the rPE-HPhA system can be used for delivering genes of interest into mammalian cells and has great potential to be applied for gene therapy. 相似文献
113.
114.
115.
116.
Wei Liu Yaoting Sun Weigang Ge Fangfei Zhang Lin Gan Yi Zhu Tiannan Guo Kexin Liu 《Molecular & cellular proteomics : MCP》2022,21(2):100187
Drug resistance is a critical obstacle to effective treatment in patients with chronic myeloid leukemia. To understand the underlying resistance mechanisms in response to imatinib mesylate (IMA) and adriamycin (ADR), the parental K562 cells were treated with low doses of IMA or ADR for 2 months to generate derivative cells with mild, intermediate, and severe resistance to the drugs as defined by their increasing resistance index. PulseDIA-based (DIA [data-independent acquisition]) quantitative proteomics was then employed to reveal the proteome changes in these resistant cells. In total, 7082 proteins from 98,232 peptides were identified and quantified from the dataset using four DIA software tools including OpenSWATH, Spectronaut, DIA-NN, and EncyclopeDIA. Sirtuin signaling pathway was found to be significantly enriched in both ADR-resistant and IMA-resistant K562 cells. In particular, isocitrate dehydrogenase (NADP(+)) 2 was identified as a potential drug target correlated with the drug resistance phenotype, and its inhibition by the antagonist AGI-6780 reversed the acquired resistance in K562 cells to either ADR or IMA. Together, our study has implicated isocitrate dehydrogenase (NADP(+)) 2 as a potential target that can be therapeutically leveraged to alleviate the drug resistance in K562 cells when treated with IMA and ADR. 相似文献
117.
118.
Distinct effects of climate warming on populations of silver fir (Abies alba) across Europe
下载免费PDF全文
![点击此处可从《Journal of Biogeography》网站下载免费的PDF全文](/ch/ext_images/free.gif)
119.
Mingcheng Qian Xinyu Jiang Mingting Zhang Lijuan Hu Huimin Liu Shuai Zhao Xiaoying Zhou Xin Chen 《化学与生物多样性》2021,18(4):e2000979
In this article, we designed and synthesized two series of matrine analogs with ring-opening in the lactam portion of the molecule. Our in vitro cytotoxicity study showed that analog N-(3-bromophenyl)-4-[(1R,3aS,10aR,10bS)-decahydro-1H,4H-pyrido[3,2,1-ij][1,6]naphthyridin-1-yl]butanamide ( B11 ) with a meta-bromide on the phenyl ring displayed the best antiproliferative activity. Moreover, B11 induced cell cycle arrest in G1 phase and cell apoptosis in a dose-dependent manner in A549 cells. Molecular modeling revealed that B11 achieved a higher docking score compared to its precursor tert-butyl (1R,3aS,10aR,10bS)-1-[4-(3-bromoanilino)-4-oxobutyl]octahydro-1H,4H-pyrido[3,2,1-ij][1,6]naphthyridine-2(3H)-carboxylate ( A11 , an analog of B11 with a Boc group) and parent compound matrine, possibly because B11 formed a hydrogen bond with SER91 and a halogen bond with GLN320 on the binding site of annexin A2. Overall, we discovered the potential anticancer lead compound B11 , which can be used for further study both in vitro and in vivo. 相似文献
120.