全文获取类型
收费全文 | 5145篇 |
免费 | 437篇 |
国内免费 | 297篇 |
专业分类
5879篇 |
出版年
2024年 | 11篇 |
2023年 | 50篇 |
2022年 | 127篇 |
2021年 | 210篇 |
2020年 | 132篇 |
2019年 | 183篇 |
2018年 | 216篇 |
2017年 | 142篇 |
2016年 | 234篇 |
2015年 | 323篇 |
2014年 | 375篇 |
2013年 | 330篇 |
2012年 | 460篇 |
2011年 | 431篇 |
2010年 | 263篇 |
2009年 | 250篇 |
2008年 | 273篇 |
2007年 | 255篇 |
2006年 | 217篇 |
2005年 | 201篇 |
2004年 | 187篇 |
2003年 | 167篇 |
2002年 | 168篇 |
2001年 | 100篇 |
2000年 | 70篇 |
1999年 | 70篇 |
1998年 | 62篇 |
1997年 | 42篇 |
1996年 | 40篇 |
1995年 | 37篇 |
1994年 | 32篇 |
1993年 | 23篇 |
1992年 | 22篇 |
1991年 | 27篇 |
1990年 | 23篇 |
1989年 | 21篇 |
1988年 | 10篇 |
1987年 | 9篇 |
1986年 | 16篇 |
1985年 | 16篇 |
1983年 | 9篇 |
1982年 | 6篇 |
1981年 | 10篇 |
1980年 | 3篇 |
1979年 | 5篇 |
1978年 | 3篇 |
1976年 | 2篇 |
1972年 | 5篇 |
1971年 | 3篇 |
1969年 | 3篇 |
排序方式: 共有5879条查询结果,搜索用时 15 毫秒
991.
Siyuan Zhang Jinhong Kan Xin Liu Yao Wu Mingyang Zhang Jinqing Ou Juan Wang Lin An Defeng Li Li Wang Xiu-Jie Wang Rongxiang Fang Yantao Jia 《Molecular Plant Pathology》2023,24(4):359-373
Chemical signal-mediated biological communication is common within bacteria and between bacteria and their hosts. Many plant-associated bacteria respond to unknown plant compounds to regulate bacterial gene expression. However, the nature of the plant compounds that mediate such interkingdom communication and the underlying mechanisms remain poorly characterized. Xanthomonas campestris pv. campestris (Xcc) causes black rot disease on brassica vegetables. Xcc contains an orphan LuxR regulator (XccR) which senses a plant signal that was validated to be glucose by HPLC-MS. The glucose concentration increases in apoplast fluid after Xcc infection, which is caused by the enhanced activity of plant sugar transporters translocating sugar and cell-wall invertases releasing glucose from sucrose. XccR recruits glucose, but not fructose, sucrose, glucose 6-phosphate, and UDP-glucose, to activate pip expression. Deletion of the bacterial glucose transporter gene sglT impaired pathogen virulence and pip expression. Structural prediction showed that the N-terminal domain of XccR forms an alternative pocket neighbouring the AHL-binding pocket for glucose docking. Substitution of three residues affecting structural stability abolished the ability of XccR to bind to the luxXc box in the pip promoter. Several other XccR homologues from plant-associated bacteria can also form stable complexes with glucose, indicating that glucose may function as a common signal molecule for pathogen–plant interactions. The conservation of a glucose/XccR/pip-like system in plant-associated bacteria suggests that some phytopathogens have evolved the ability to utilize host compounds as virulence signals, indicating that LuxRs mediate an interkingdom signalling circuit. 相似文献
992.
Favre J Gao J Zhang AD Remy-Jouet I Ouvrard-Pascaud A Dautreaux B Escoubet B Thuillez C Jaisser F Richard V 《American journal of physiology. Heart and circulatory physiology》2011,300(6):H2035-H2043
The deleterious effects of aldosterone excess demonstrated in cardiovascular diseases might be linked in part to coronary vascular dysfunction. However, whether such vascular dysfunction is a cause or a consequence of the changes occurring in the cardiomyocytes is unclear. Moreover, the possible link between mineralocorticoid receptor (MR)-mediated effects on the cardiomyocyte and the coronary arteries is unknown. Thus we used a mouse model with conditional, cardiomyocyte-specific overexpression of human MR (hMR) and observed the effects on endothelial function in isolated coronary segments. hMR overexpression decreased the nitric oxide (NO)-mediated relaxing responses to acetylcholine in coronary arteries (but not in peripheral arteries), and this was prevented by a 1-mo treatment either with an MR antagonist, vitamin E/vitamin C, or a NADPH oxidase inhibitor. hMR overexpression did not affect coronary endothelial NO synthase content nor its level of phosphorylation on serine 1177, but increased cardiac levels of reactive oxygen species, cardiac NADPH oxidase (NOX) activity, and expression of the NOX subunit gp91phox, which was limited to endothelial cells. Thus an increase in hMR activation, restricted to cardiomyocytes, is sufficient to induce a severe coronary endothelial dysfunction. We suggest a new paracrine mechanism by which cardiomyocytes trigger a NOX-dependent, reactive oxygen species-mediated coronary endothelial dysfunction. 相似文献
993.
Liana Tsiatsiani Evy Timmerman Pieter-Jan De Bock Dominique Vercammen Simon Stael Brigitte van de Cotte An Staes Marc Goethals Tine Beunens Petra Van Damme Kris Gevaert Frank Van Breusegem 《The Plant cell》2013,25(8):2831-2847
Metacaspases are distant relatives of the metazoan caspases, found in plants, fungi, and protists. However, in contrast with caspases, information about the physiological substrates of metacaspases is still scarce. By means of N-terminal combined fractional diagonal chromatography, the physiological substrates of METACASPASE9 (MC9; AT5G04200) were identified in young seedlings of Arabidopsis thaliana on the proteome-wide level, providing additional insight into MC9 cleavage specificity and revealing a previously unknown preference for acidic residues at the substrate prime site position P1′. The functionalities of the identified MC9 substrates hinted at metacaspase functions other than those related to cell death. These results allowed us to resolve the substrate specificity of MC9 in more detail and indicated that the activity of phosphoenolpyruvate carboxykinase 1 (AT4G37870), a key enzyme in gluconeogenesis, is enhanced upon MC9-dependent proteolysis. 相似文献
994.
Shu-Yan Li Wen-Ge Sun Yu-Hong Jia Guo-Sheng Wu Guo-Shun An Ju-Hua Ni Hong-Ti Jia 《Biochemistry. Biokhimii?a》2010,75(1):101-110
We demonstrate that activation of nuclear factor κB (NF-κB) in neurons is neuroprotective in response to kainic acid (KA)-induced
excitotoxicity. Combination of Western blotting, immunocytochemistry, and electrophoresis mobility shift assay showed that
KA exposure induced a fast but transient nuclear translocation of the NF-κB p65 subunit and increased DNA-binding activity
of NF-κB in primary cultured cortical neurons. The transient NF-κB activity was associated with upregulation of antiapoptotic
Bcl-xL and XIAP gene products revealed by real-time PCR. Knockdown of p65 decreased neuronal viability and antiapoptotic gene
expression. In addition, we showed that KA-stimulated DNA-binding activity of NF-κB was associated with reactive oxygen species
and calcium signals, using AMPA/KA receptor antagonist, calcium chelator, and antioxidant. These results suggest that the
fast and transient activation of NF-κB initiated by calcium signals is one of the important proximal events in response to
KA-induced excitotoxicity, which has neuroprotective effect against KA-induced apoptosis. 相似文献
995.
Kim DW Yoon CS Eum WS Lee BR An JJ Lee SH Lee SR Ahn JY Kwon OS Kang TC Won MH Cho SW Lee KS Park J Choi SY 《Molecules and cells》2004,18(3):314-319
gamma-Aminobutyrate transaminase (GABA-T), a key enzyme of the GABA shunt, converts the major inhibitory neurotransmitter, GABA, to succinic semialdehyde. Although GABA-T is a pivotal factor implicated in the pathogenesis of various neurological disorders, its function remains to be elucidated. In an effort to clarify the structural and functional roles of specific lysyl residue in human brain GABA-T, we constructed human brain GABA-T mutants, in which the lysyl residue at position 357 was mutated to various amino acids including asparagine (K357N). The purified mutant GABA-T enzymes displayed neither catalytic activity nor absorption bands at 330 and 415 nm that are characteristic of pyridoxal-5'-phosphate (PLP) covalently linked to the protein. The wild type apoenzyme reconstituted with exogenous PLP had catalytic activity, while the mutant apoenzymes did not. These results indicate that lysine 357 is essential for catalytic function, and is involved in binding PLP at the active site. 相似文献
996.
Shuhuai Yu Lanjun Zhu Chen Zhou Tao An Tao Zhang Bo Jiang Wanmeng Mu 《Applied microbiology and biotechnology》2014,98(4):1621-1630
The cDNA gene coding for formate dehydrogenase (FDH) from Ogataea parapolymorpha DL-1 was cloned and expressed in Escherichia coli. The recombinant enzyme was purified by nickel affinity chromatography and was characterized as a homodimer composed of two identical subunits with approximately 40 kDa in each monomer. The enzyme showed wide pH optimum of catalytic activity from pH 6.0 to 7.0. It had relatively high optimum temperature at 65 °C and retained 93, 88, 83, and 71 % of its initial activity after 4 h of exposure at 40, 50, 55, and 60 °C, respectively, suggesting that this enzyme had promising thermal stability. In addition, the enzyme was characterized to have significant tolerance ability to organic solvents such as dimethyl sulfoxide, n-butanol, and n-hexane. The Michaelis–Menten constant (K m), turnover number (k cat), and catalytic efficiency (k cat/K m) values of the enzyme for the substrate sodium formate were estimated to be 0.82 mM, 2.32 s?1, and 2.83 mM?1 s?1, respectively. The K m for NAD+ was 83 μM. Due to its wide pH optimum, promising thermostability, and high organic solvent tolerance, O. parapolymorpha FDH may be a good NADH regeneration catalyst candidate. 相似文献
997.
Identification of the phosphorylation targets of symbiotic receptor‐like kinases using a high‐throughput multiplexed assay for kinase specificity
下载免费PDF全文
![点击此处可从《The Plant journal : for cell and molecular biology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Dhileepkumar Jayaraman Alicia L. Richards Michael S. Westphall Joshua J. Coon Jean‐Michel Ané 《The Plant journal : for cell and molecular biology》2017,90(6):1196-1207
Detecting the phosphorylation substrates of multiple kinases in a single experiment is a challenge, and new techniques are being developed to overcome this challenge. Here, we used a multiplexed assay for kinase specificity (MAKS) to identify the substrates directly and to map the phosphorylation site(s) of plant symbiotic receptor‐like kinases. The symbiotic receptor‐like kinases nodulation receptor‐like kinase (NORK) and lysin motif domain‐containing receptor‐like kinase 3 (LYK3) are indispensable for the establishment of root nodule symbiosis. Although some interacting proteins have been identified for these symbiotic receptor‐like kinases, very little is known about their phosphorylation substrates. Using this high‐throughput approach, we identified several other potential phosphorylation targets for both these symbiotic receptor‐like kinases. In particular, we also discovered the phosphorylation of LYK3 by NORK itself, which was also confirmed by pairwise kinase assays. Motif analysis of potential targets for these kinases revealed that the acidic motif xxxsDxxx was common to both of them. In summary, this high‐throughput technique catalogs the potential phosphorylation substrates of multiple kinases in a single efficient experiment, the biological characterization of which should provide a better understanding of phosphorylation signaling cascade in symbiosis. 相似文献
998.
999.
1000.