全文获取类型
收费全文 | 3579篇 |
免费 | 208篇 |
国内免费 | 194篇 |
出版年
2023年 | 60篇 |
2022年 | 67篇 |
2021年 | 113篇 |
2020年 | 98篇 |
2019年 | 148篇 |
2018年 | 153篇 |
2017年 | 103篇 |
2016年 | 77篇 |
2015年 | 76篇 |
2014年 | 234篇 |
2013年 | 277篇 |
2012年 | 194篇 |
2011年 | 223篇 |
2010年 | 148篇 |
2009年 | 154篇 |
2008年 | 141篇 |
2007年 | 166篇 |
2006年 | 150篇 |
2005年 | 121篇 |
2004年 | 93篇 |
2003年 | 113篇 |
2002年 | 69篇 |
2001年 | 51篇 |
2000年 | 50篇 |
1999年 | 36篇 |
1998年 | 30篇 |
1997年 | 46篇 |
1996年 | 32篇 |
1995年 | 23篇 |
1994年 | 22篇 |
1993年 | 25篇 |
1992年 | 40篇 |
1991年 | 39篇 |
1990年 | 27篇 |
1989年 | 20篇 |
1988年 | 25篇 |
1987年 | 22篇 |
1985年 | 45篇 |
1984年 | 76篇 |
1983年 | 52篇 |
1982年 | 51篇 |
1981年 | 44篇 |
1980年 | 55篇 |
1979年 | 43篇 |
1978年 | 24篇 |
1977年 | 26篇 |
1976年 | 24篇 |
1975年 | 23篇 |
1974年 | 16篇 |
1973年 | 17篇 |
排序方式: 共有3981条查询结果,搜索用时 531 毫秒
121.
122.
The removal of cobalt from cobalt(II) bovine carbonic anhydrase by pyridine-2-carboxylate, pyridine-2,6-dicarboxylate and 5-methyl-1,10-phenanthroline occurs via formation of an intermediate. This is presumed to be a ternary adduct of cobalt(II) enzyme with the ligand. In this, metal-protein bonds are loosened, probably via distortion of the normal geometry, resulting in accelerated breakdown of the adduct to apoprotein, compared with the behavior of the cobalt(II) enzyme alone. With 2-carboxy-1,10-phenanthroline, removal of metal is very rapid but no adduct is observed. Values of stability constants of the adducts and rate constants for their decomposition to apoprotein and their formation from apoprotein and cobalt(II) complex were measured at pH 5.5 and 25°C. Formation and dissociation rate constants for the adduct of cobalt carbonic anhydrase with pyridine-2,6-dicarboxylate could be measured from pH 5 to 7 and 10° to 25°C by stopped flow. Values of thermodynamic parameters for the various reactions agreed well with those estimated from the kinetic data. 相似文献
123.
124.
125.
《Journal of structural biology》2020,209(1):107399
G-quadruplexes (G4) are secondary structures of nucleic acids that can form in cells and have diverse biological functions. Several biologically important proteins interact with G-quadruplexes, of which RHAU (or DHX36) – a helicase from the DEAH-box superfamily, was shown to bind and unwind G-quadruplexes efficiently. We report a X-ray co-crystal structure at 1.5 Å resolution of an N-terminal fragment of RHAU bound to an exposed tetrad of a parallel-stranded G-quadruplex. The RHAU peptide folds into an L-shaped α-helix, and binds to a G-quadruplex through π-stacking and electrostatic interactions. X-ray crystal structure of our complex identified key amino acid residues important for G-quadruplex-peptide binding interaction at the 3′-end G•G•G•G tetrad. Together with previous solution and crystal structures of RHAU bound to the 5′-end G•G•G•G and G•G•A•T tetrads, our crystal structure highlights the occurrence of a robust G-quadruplex recognition motif within RHAU that can adapt to different accessible tetrads. 相似文献
126.
127.
《基因组蛋白质组与生物信息学报(英文版)》2020,18(2):161-172
Genome reannotation aims for complete and accurate characterization of gene models and thus is of critical significance for in-depth exploration of gene function. Although the availability of massive RNA-seq data provides great opportunities for gene model refinement, few efforts have been made to adopt these precious data in rice genome reannotation. Here we reannotate the rice (Oryza sativa L. ssp. japonica) genome based on integration of large-scale RNA-seq data and release a new annotation system IC4R-2.0. In general, IC4R-2.0 significantly improves the completeness of gene structure, identifies a number of novel genes, and integrates a variety of functional annotations. Furthermore, long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) are systematically characterized in the rice genome. Performance evaluation shows that compared to previous annotation systems, IC4R-2.0 achieves higher integrity and quality, primarily attributable to massive RNA-seq data applied in genome annotation. Consequently, we incorporate the improved annotations into the Information Commons for Rice (IC4R), a database integrating multiple omics data of rice, and accordingly update IC4R by providing more user-friendly web interfaces and implementing a series of practical online tools. Together, the updated IC4R, which is equipped with the improved annotations, bears great promise for comparative and functional genomic studies in rice and other monocotyledonous species. The IC4R-2.0 annotation system and related resources are freely accessible at http://ic4r.org/. 相似文献
128.
Yuan Xiong Chenchen Yan Lang Chen Yori Endo Yun Sun Wu Zhou Yiqiang Hu Liangcong Hu Dong Chen Hang Xue Bobin Mi Guohui Liu 《Journal of cellular and molecular medicine》2020,24(1):1076-1086
Interleukin‐10 (IL‐10) displays well‐documented anti‐inflammatory effects, but its effects on osteoblast differentiation have not been investigated. In this study, we found IL‐10 negatively regulates microRNA‐7025‐5p (miR‐7025‐5p), the down‐regulation of which enhances osteoblast differentiation. Furthermore, through luciferase reporter assays, we found evidence that insulin‐like growth factor 1 receptor (IGF1R) is a miR‐7025‐5p target gene that positively regulates osteoblast differentiation. In vivo studies indicated that the pre‐injection of IL‐10 leads to increased bone formation, while agomiR‐7025‐5p injection delays fracture healing. Taken together, these results indicate that IL‐10 induces osteoblast differentiation via regulation of the miR‐7025‐5p/IGF1R axis. IL‐10 therefore represents a promising therapeutic strategy to promote fracture healing. 相似文献
129.
Zhiyong Fan Yinghui Liu Zhengliang Shi Kai Deng Hua Zhang Qiutong Li Shuxing Cao Shentai Li Hongliang Zhang 《Journal of cellular and molecular medicine》2020,24(15):8441-8451
Osteoarthritis (OA) is a common joint disease characterized by progressive cartilage degradation, in which elevated chondrocyte apoptosis and catabolic activity play an important role. MicroRNA‐155 (miR‐155) has recently been shown to regulate apoptosis and catabolic activity in some pathological circumstances, yet, whether and how miR‐155 is associated with OA pathology remain unexplored. We report here that miR‐155 level is significantly up‐regulated in human OA cartilage biopsies and also in primary chondrocytes stimulated by interleukin‐1β (IL‐1β), a pivotal pro‐catabolic factor promoting cartilage degradation. Moreover, miR‐155 inhibition attenuates and its overexpression promotes IL‐1β‐induced apoptosis and catabolic activity in chondrocytes in vitro. We also demonstrate that the PIK3R1 (p85α regulatory subunit of phosphoinositide 3‐kinase (PI3K)) is a target of miR‐155 in chondrocytes, and more importantly, PIK3R1 restoration abrogates miR‐155 effects on chondrocyte apoptosis and catabolic activity. Mechanistically, PIK3R1 positively regulates the transduction of PI3K/Akt pathway, and a specific Akt inhibitor reverses miR‐155 effects on promoting chondrocyte apoptosis and catabolic activity, phenocopying the results obtained via PIK3R1 knockdown, hence establishing that miR‐155 promotes chondrocyte apoptosis and catabolic activity through targeting PIK3R1‐mediated PI3K/Akt pathway activation. Altogether, our study discovers novel roles and mechanisms of miR‐155 in regulating chondrocyte apoptosis and catabolic activity, providing an implication for therapeutically intervening cartilage degradation and OA progression. 相似文献
130.
Neekun Sharma Anthony M. Belenchia Ryan Toedebusch Lakshmi Pulakat Chetan P. Hans 《Journal of cellular and molecular medicine》2020,24(13):7393-7404
Clinical and experimental studies show that angiotensin II (AngII) promotes vascular pathology via activation of AngII type 1 receptors (AT1Rs). We recently reported that NP‐6A4, a selective peptide agonist for AngII type 2 receptor (AT2R), exerts protective effects on human vascular cells subjected to serum starvation or doxorubicin exposure. In this study, we investigated whether NP‐6A4–induced AT2R activation could mitigate AngII‐induced abdominal aortic aneurism (AAA) using AngII‐treated Apoe?/? mice. Male Apoe?/? mice were infused with AngII (1 µg/kg/min) by implanting osmotic pumps subcutaneously for 28 days. A subset of mice was pre‐treated subcutaneously with NP‐6A4 (2.5 mg/kg/day) or vehicle for 14 days prior to AngII, and treatments were continued for 28 days. NP‐6A4 significantly reduced aortic stiffness of the abdominal aorta induced by AngII as determined by ultrasound functional analyses and histochemical analyses. NP‐6A4 also increased nitric oxide bioavailability in aortic tissues and suppressed AngII‐induced increases in monocyte chemotactic protein‐1, osteopontin and proteolytic activity of the aorta. However, NP‐6A4 did not affect maximal intraluminal aortic diameter or AAA incidences significantly. These data suggest that the effects of AT2R agonist on vascular pathologies are selective, affecting the aortic stiffness and proteolytic activity without affecting the size of AAA. 相似文献