全文获取类型
收费全文 | 4414篇 |
免费 | 380篇 |
国内免费 | 275篇 |
专业分类
5069篇 |
出版年
2024年 | 11篇 |
2023年 | 46篇 |
2022年 | 135篇 |
2021年 | 231篇 |
2020年 | 165篇 |
2019年 | 186篇 |
2018年 | 201篇 |
2017年 | 133篇 |
2016年 | 183篇 |
2015年 | 286篇 |
2014年 | 353篇 |
2013年 | 329篇 |
2012年 | 413篇 |
2011年 | 349篇 |
2010年 | 210篇 |
2009年 | 223篇 |
2008年 | 252篇 |
2007年 | 197篇 |
2006年 | 161篇 |
2005年 | 134篇 |
2004年 | 109篇 |
2003年 | 119篇 |
2002年 | 111篇 |
2001年 | 80篇 |
2000年 | 72篇 |
1999年 | 52篇 |
1998年 | 28篇 |
1997年 | 35篇 |
1996年 | 37篇 |
1995年 | 43篇 |
1994年 | 33篇 |
1993年 | 24篇 |
1992年 | 27篇 |
1991年 | 22篇 |
1990年 | 17篇 |
1989年 | 14篇 |
1988年 | 8篇 |
1987年 | 8篇 |
1986年 | 9篇 |
1985年 | 3篇 |
1984年 | 6篇 |
1983年 | 5篇 |
1982年 | 2篇 |
1981年 | 1篇 |
1980年 | 1篇 |
1975年 | 1篇 |
1973年 | 1篇 |
1971年 | 1篇 |
1970年 | 1篇 |
1967年 | 1篇 |
排序方式: 共有5069条查询结果,搜索用时 15 毫秒
951.
Lei Zhang Ge Song Ting Xu Qing-Ping Wu Xiao-Xia Shao Ya-Li Liu Zeng-Guang Xu Zhan-Yun Guo 《Biochimie》2013
Insulin-like peptide 3 (INSL3) is a reproduction-related peptide hormone belonging to the insulin/relaxin superfamily, which mediates testicular descent in the male fetus, suppresses male germ cell apoptosis and promotes oocyte maturation in adults by activating the relaxin family peptide receptor 2 (RXFP2). To establish an ultrasensitive receptor-binding assay for INSL3−RXFP2 interaction studies, in the present work we labeled a recombinant INSL3 peptide with a newly developed nanoluciferase (NanoLuc) reporter through a convenient chemical conjugation approach, including the introduction of an active disulfide bond to INSL3 by chemical modification and engineering of a 6× His-Cys-NanoLuc carrying a unique exposed cysteine at the N-terminus. The bioluminescent NanoLuc-conjugated INSL3 retained high binding affinity with the target receptor RXFP2 (Kd = 2.0 ± 0.1 nM, n = 3) and was able to sensitively monitor the receptor-binding of a variety of ligands, representing a novel ultrasensitive tracer for non-radioactive receptor-binding assays. Our present chemical conjugation approach could readily be adapted for conjugation of NanoLuc with other proteins, even other macrobiomolecules, for various highly sensitive bioluminescent assays. 相似文献
952.
目的为了及时诊断产后出血和正确测量剖宫产术中的失血量,及时补充血容量,降低孕产妇死亡率。方法同一剖宫术孕妇分别采用精测法(称重法和液血分流吸引器相结合)和目测法两种方法进行失血量的比较。结果目测法估算失血量明显低于精测法,结果显示用精测法对剖宫产术中进行失血量的估算是目测法的1.5倍(1.5:1)。结论在剖宫产术中精确测量失血量,及时诊断产后出血,有利于及时补充血容量,提高孕产妇身心健康。 相似文献
953.
Xiaozhen Wang Guang Lu Li Li Juan Yi Kaowen Yan Yaqing Wang Baili Zhu Jingyu Kuang Ming Lin Sha Zhang Genze Shao 《Biochemical and biophysical research communications》2014
The cellular BRCA1 protein level is essential for its tumor suppression activity and is tightly regulated through multiple mechanisms including ubiquitn–proteasome system. E3 ligases are involved to promote BRCA1 for ubiquitination and degradation. Here, we identified HUWE1/Mule/ARF-BP1 as a novel BRCA1-interacting protein involved in the control of BRCA1 protein level. HUWE1binds BRCA1 through its N-terminus degron domain. Depletion of HUWE1 by siRNA-mediated interference significantly increases BRCA1 protein levels and prolongs the half-life of BRCA1. Moreover, exogenous expression of HUWE1 promotes BRCA1 degradation through the ubiquitin–proteasome pathway, which could explain an inverse correlation between HUWE1 and BRCA1 levels in MCF10F, MCF7 and MDA-MB-231 breast cancer cells. Consistent with a functional role for HUWE1 in regulating BRCA1-mediated cellular response to DNA damage, depletion of HUWE1 by siRNA confers increased resistance to ionizing radiation and mitomycin. These data indicate that HUWE1 is a critical negative regulator of BRCA1 and suggest a new molecular mechanism for breast cancer pathogenesis. 相似文献
954.
955.
A specific signaling role for H2O2 in Chlamydomonas reinhardtii was demonstrated by the definition of a promoter that specifically responded to this ROS. Expression of a nuclear-encoded
reporter gene driven by this promoter was shown to depend not only on the level of exogenously added H2O2 but also on light. In the dark, the induction of the reporter gene by H2O2 was much lower than in the light. This lower induction was correlated with an accelerated disappearance of H2O2 from the culture medium in the dark. Due to a light-induced reduction in catalase activity, H2O2 levels in the light remained higher. Photosynthetic electron transport mediated the light-controlled down-regulation of the
catalase activity since it was prevented by 3-(3′4′-dichlorophenyl)-1,1-dimethylurea (DCMU), an inhibitor of photosystem II.
In the presence of light and DCMU, expression of the reporter gene was low while the addition of aminotriazole, a catalase
inhibitor, led to a higher induction of the reporter gene by H2O2 in the dark. The role of photosynthetic electron transport and thioredoxin in this regulation was investigated by using mutants
deficient in photosynthetic electron flow and by studying the correlation between NADP-malate dehydrogenase and catalase activities.
It is proposed that, contrary to expectations, a controlled down-regulation of catalase activity occurs upon a shift of cells
from dark to light. This down-regulation apparently is necessary to maintain a certain level of H2O2 required to activate H2O2-dependent signaling pathways. 相似文献
956.
Qingxia Fang Ting Liu Chenhuan Yu Xiuli Yang Yanfei Shao Jiana Shi Xiaolan Ye Xiaochun Zheng Jieping Yan Danfeng Xu Xiaozhou Zou 《Journal of cellular and molecular medicine》2020,24(6):3678-3691
The current study was designed to explore the role and underlying mechanism of lncRNA taurine up-regulated gene 1 (TUG1) in cardiac hypertrophy. Mice were treated by transverse aortic constriction (TAC) surgery to induce cardiac hypertrophy, and cardiomyocytes were treated by phenylephrine (PE) to induce hypertrophic phenotype. Haematoxylin-eosin (HE), wheat germ agglutinin (WGA) and immunofluorescence (IF) were used to examine morphological alterations. Real-time PCR, Western blots and IF staining were used to detect the expression of RNAs and proteins. Luciferase assay and RNA pull-down assay were used to verify the interaction. It is revealed that TUG1 was up-regulated in the hearts of mice treated by TAC surgery and in PE-induced cardiomyocytes. Functionally, overexpression of TUG1 alleviated cardiac hypertrophy both in vivo and in vitro. Mechanically, TUG1 sponged and sequestered miR-34a to increase the Dickkopf 1 (DKK1) level, which eventually inhibited the activation of Wnt/β-catenin signalling. In conclusion, the current study reported the protective role and regulatory mechanism of TUG1 in cardiac hypertrophy and suggested that TUG1 may serve as a novel molecular target for treating cardiac hypertrophy. 相似文献
957.
Ultrafiltration is used to remove small impurities from a variety of processing streams. However, the clearance of small charged impurities may be inadequate due to electrostatic exclusion by the charged ultrafiltration membranes, an effect that has been largely unappreciated. Ultrafiltration experiments were performed to evaluate the transmission of several model impurities with different electrical charge through ultrafiltration membranes having different surface charge characteristics. Highly charged impurities are strongly rejected by charged cellulose and polyethersulfone membranes even though these solutes are much smaller than the membrane pore size. These effects could be eliminated by using high ionic strength solutions to shield the electrostatic interactions. The sieving data are in good agreement with model calculations based on the partitioning of charged spheres into charged cylindrical pores. Guidelines are developed for estimating conditions needed to obtain effective removal of small charged impurities through charged ultrafiltration membranes. 相似文献
958.
Bonsu Ku Kwang-Hoon Lee Wei Sun Park Chul-Su Yang Jianning Ge Seong-Gyu Lee Sun-Shin Cha Feng Shao Won Do Heo Jae U. Jung Byung-Ha Oh 《PLoS pathogens》2012,8(12)
Upon phagocytosis, Legionella pneumophila translocates numerous effector proteins into host cells to perturb cellular metabolism and immunity, ultimately establishing intracellular survival and growth. VipD of L. pneumophila belongs to a family of bacterial effectors that contain the N-terminal lipase domain and the C-terminal domain with an unknown function. We report the crystal structure of VipD and show that its C-terminal domain robustly interferes with endosomal trafficking through tight and selective interactions with Rab5 and Rab22. This domain, which is not significantly similar to any known protein structure, potently interacts with the GTP-bound active form of the two Rabs by recognizing a hydrophobic triad conserved in Rabs. These interactions prevent Rab5 and Rab22 from binding to downstream effectors Rabaptin-5, Rabenosyn-5 and EEA1, consequently blocking endosomal trafficking and subsequent lysosomal degradation of endocytic materials in macrophage cells. Together, this work reveals endosomal trafficking as a target of L. pneumophila and delineates the underlying molecular mechanism. 相似文献
959.
Changwei Shao Yongchao Niu Pasi Rastas Yang Liu Zhiyuan Xie Hengde Li Lei Wang Yong Jiang Shuaishuai Tai Yongsheng Tian Takashi Sakamoto Songlin Chen 《DNA research》2015,22(2):161-170
High-resolution genetic maps are essential for fine mapping of complex traits, genome assembly, and comparative genomic analysis. Single-nucleotide polymorphisms (SNPs) are the primary molecular markers used for genetic map construction. In this study, we identified 13,362 SNPs evenly distributed across the Japanese flounder (Paralichthys olivaceus) genome. Of these SNPs, 12,712 high-confidence SNPs were subjected to high-throughput genotyping and assigned to 24 consensus linkage groups (LGs). The total length of the genetic linkage map was 3,497.29 cM with an average distance of 0.47 cM between loci, thereby representing the densest genetic map currently reported for Japanese flounder. Nine positive quantitative trait loci (QTLs) forming two main clusters for Vibrio anguillarum disease resistance were detected. All QTLs could explain 5.1–8.38% of the total phenotypic variation. Synteny analysis of the QTL regions on the genome assembly revealed 12 immune-related genes, among them 4 genes strongly associated with V. anguillarum disease resistance. In addition, 246 genome assembly scaffolds with an average size of 21.79 Mb were anchored onto the LGs; these scaffolds, comprising 522.99 Mb, represented 95.78% of assembled genomic sequences. The mapped assembly scaffolds in Japanese flounder were used for genome synteny analyses against zebrafish (Danio rerio) and medaka (Oryzias latipes). Flounder and medaka were found to possess almost one-to-one synteny, whereas flounder and zebrafish exhibited a multi-syntenic correspondence. The newly developed high-resolution genetic map, which will facilitate QTL mapping, scaffold assembly, and genome synteny analysis of Japanese flounder, marks a milestone in the ongoing genome project for this species. 相似文献
960.
细胞表面构图技术对于研究细胞以及细胞间相互作用具有重要意义。近年来随着微加工技术与表面修饰技术的发展,出现了多种细胞表面构图方法。本研究介绍一种基于微流控芯片和电化学自组装单层修饰的多细胞表面构图方法。该方法通过软光刻技术加工具有2种细胞拦截坝结构阵列的微流控通道来实现2种细胞在芯片表面准确定位;通过表面修饰具有阻碍细胞贴壁特性自组装单层来实现对细胞生长区域的限制;最终实现2种不同细胞近距离表面构图。该方法的优点在于,可以使多种细胞根据需要进行准确的表面构图,细胞区域之间没有物理隔离共享培养微环境,允许不同种细胞通过细胞分泌因子进行相互作用,基底透明表面开放可以使用多种观测手段。该方法可以用于不同种细胞间相互作用的研究。 相似文献