全文获取类型
收费全文 | 28669篇 |
免费 | 2410篇 |
国内免费 | 2111篇 |
专业分类
33190篇 |
出版年
2024年 | 67篇 |
2023年 | 361篇 |
2022年 | 834篇 |
2021年 | 1388篇 |
2020年 | 889篇 |
2019年 | 1093篇 |
2018年 | 1058篇 |
2017年 | 776篇 |
2016年 | 1131篇 |
2015年 | 1706篇 |
2014年 | 1979篇 |
2013年 | 2105篇 |
2012年 | 2623篇 |
2011年 | 2237篇 |
2010年 | 1426篇 |
2009年 | 1129篇 |
2008年 | 1548篇 |
2007年 | 1322篇 |
2006年 | 1209篇 |
2005年 | 1016篇 |
2004年 | 863篇 |
2003年 | 744篇 |
2002年 | 667篇 |
2001年 | 574篇 |
2000年 | 459篇 |
1999年 | 526篇 |
1998年 | 292篇 |
1997年 | 246篇 |
1996年 | 276篇 |
1995年 | 227篇 |
1994年 | 276篇 |
1993年 | 170篇 |
1992年 | 264篇 |
1991年 | 238篇 |
1990年 | 216篇 |
1989年 | 141篇 |
1988年 | 121篇 |
1987年 | 119篇 |
1986年 | 93篇 |
1985年 | 104篇 |
1984年 | 72篇 |
1983年 | 67篇 |
1982年 | 60篇 |
1981年 | 41篇 |
1980年 | 38篇 |
1979年 | 51篇 |
1978年 | 40篇 |
1977年 | 36篇 |
1976年 | 37篇 |
1973年 | 37篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
51.
52.
J C Shih R H Chiu Y L Chan 《Biochemical and biophysical research communications》1976,68(4):1348-1355
Some properties of histidine:pyruvate transaminase (HPT) and phenylalanine:pyruvate transaminase (PPT) in the cytosol of rat liver were studied. HPT and PPT activity could not be separated by DEAE-Sephadex A-50 or hydroxylapatite column chromatography, and the ratio of activity remained constant during these purification procedures. The two enzyme activities also showed similar heat stability and responses to glucagon injection. Based on these findings, we suggest that a single enzyme may specifically catalyze histidine:pyruvate and phenylalanine:pyruvate transamination. 相似文献
53.
The lesions induced in Bacillus subtilis deoxyribonucleic acid (DNA) after treating bacterial cells (in vivo) and bacterial DNA (in vitro) with chloramine were studied biologically and physically. Single-strand breaks and a few double-strand scissions (at higher chloramine doses) accompanied loss of DNA-transforming activity in both kinds of treatments. Chloramine was about three times more efficient in vitro than in vivo in inducing DNA single-strand breaks. DNA was slowly chlorinated; the subsequent efficiency of producing DNA breaks was high. Chlorination of cells also reduced activity of endonucleases in cells; however, chlorinated DNA of both treatments was sensitized to cleavage by endonucleases. The procedure of extracting DNA from cells treated with chloramine induced further DNA degradation. Both treatments introduced a small fraction of alkali-sensitive lesions in DNA. DNA chlorinated in vitro showed further reduction in transforming activity as well as further degradation after incubation at 50 C for 5 h whereas DNA extracted from chloramine-treated cells did not show such a heat sensitivity. 相似文献
54.
55.
56.
Hamid Alinejad-Rokny Rassa Ghavami Modegh Hamid R. Rabiee Ehsan Ramezani Sarbandi Narges Rezaie Kin Tung Tam Alistair R. R. Forrest 《PLoS computational biology》2022,18(6)
Hi-C is a genome-wide chromosome conformation capture technology that detects interactions between pairs of genomic regions and exploits higher order chromatin structures. Conceptually Hi-C data counts interaction frequencies between every position in the genome and every other position. Biologically functional interactions are expected to occur more frequently than transient background and artefactual interactions. To identify biologically relevant interactions, several background models that take biases such as distance, GC content and mappability into account have been proposed. Here we introduce MaxHiC, a background correction tool that deals with these complex biases and robustly identifies statistically significant interactions in both Hi-C and capture Hi-C experiments. MaxHiC uses a negative binomial distribution model and a maximum likelihood technique to correct biases in both Hi-C and capture Hi-C libraries. We systematically benchmark MaxHiC against major Hi-C background correction tools including Hi-C significant interaction callers (SIC) and Hi-C loop callers using published Hi-C, capture Hi-C, and Micro-C datasets. Our results demonstrate that 1) Interacting regions identified by MaxHiC have significantly greater levels of overlap with known regulatory features (e.g. active chromatin histone marks, CTCF binding sites, DNase sensitivity) and also disease-associated genome-wide association SNPs than those identified by currently existing models, 2) the pairs of interacting regions are more likely to be linked by eQTL pairs and 3) more likely to link known regulatory features including known functional enhancer-promoter pairs validated by CRISPRi than any of the existing methods. We also demonstrate that interactions between different genomic region types have distinct distance distributions only revealed by MaxHiC. MaxHiC is publicly available as a python package for the analysis of Hi-C, capture Hi-C and Micro-C data. 相似文献
57.
Aaron Mendez-Bermudez Liudmyla Lototska Melanie Pousse Florent Tessier Oliver Croce Chrysa
M Latrick Veronica Cherdyntseva Joe Nassour Jiang Xiaohua Yiming Lu Corinne Abbadie Sarantis Gagos Jing Ye Eric Gilson 《Nucleic acids research》2022,50(13):7493
Cellular senescence triggers various types of heterochromatin remodeling that contribute to aging. However, the age-related mechanisms that lead to these epigenetic alterations remain elusive. Here, we asked how two key aging hallmarks, telomere shortening and constitutive heterochromatin loss, are mechanistically connected during senescence. We show that, at the onset of senescence, pericentromeric heterochromatin is specifically dismantled consisting of chromatin decondensation, accumulation of DNA breakages, illegitimate recombination and loss of DNA. This process is caused by telomere shortening or genotoxic stress by a sequence of events starting from TP53-dependent downregulation of the telomere protective protein TRF2. The resulting loss of TRF2 at pericentromeres triggers DNA breaks activating ATM, which in turn leads to heterochromatin decondensation by releasing KAP1 and Lamin B1, recombination and satellite DNA excision found in the cytosol associated with cGAS. This TP53–TRF2 axis activates the interferon response and the formation of chromosome rearrangements when the cells escape the senescent growth arrest. Overall, these results reveal the role of TP53 as pericentromeric disassembler and define the basic principles of how a TP53-dependent senescence inducer hierarchically leads to selective pericentromeric dismantling through the downregulation of TRF2. 相似文献
58.
59.
60.
Yu Shang Li Li Tengfei Zhang Qingping Luo Qingzhong Yu Zhe Zeng Lintao Li Miaomiao Jia Guoyi Tang Sanlin Fan Qin Lu Wenting Zhang Yuhan Xue Hongling Wang Wei Liu Hongcai Wang Rongrong Zhang Chan Ding Huabin Shao Guoyuan Wen 《PLoS pathogens》2022,18(6)
The development of thermostable vaccines can relieve the bottleneck of existing vaccines caused by thermal instability and subsequent poor efficacy, which is one of the predominant reasons for the millions of deaths caused by vaccine-preventable diseases. Research into the mechanism of viral thermostability may provide strategies for developing thermostable vaccines. Using Newcastle disease virus (NDV) as model, we identified the negative surface charge of attachment glycoprotein as a novel determinant of viral thermostability. It prevented the temperature-induced aggregation of glycoprotein and subsequent detachment from virion surface. Then structural stability of virion surface was improved and virus could bind to and infect cells efficiently after heat-treatment. Employing the approach of surface charge engineering, thermal stability of NDV and influenza A virus (IAV) vaccines was successfully improved. The increase in the level of vaccine thermal stability was determined by the value-added in the negative surface charge of the attachment glycoprotein. The engineered live and inactivated vaccines could be used efficiently after storage at 37°C for at least 10 and 60 days, respectively. Thus, our results revealed a novel surface-charge-mediated link between HN protein and NDV thermostability, which could be used to design thermal stable NDV and IAV vaccines rationally. 相似文献