全文获取类型
收费全文 | 617篇 |
免费 | 58篇 |
国内免费 | 3篇 |
出版年
2024年 | 1篇 |
2023年 | 10篇 |
2022年 | 12篇 |
2021年 | 15篇 |
2020年 | 9篇 |
2019年 | 17篇 |
2018年 | 16篇 |
2017年 | 18篇 |
2016年 | 21篇 |
2015年 | 28篇 |
2014年 | 43篇 |
2013年 | 40篇 |
2012年 | 62篇 |
2011年 | 44篇 |
2010年 | 25篇 |
2009年 | 32篇 |
2008年 | 31篇 |
2007年 | 31篇 |
2006年 | 34篇 |
2005年 | 34篇 |
2004年 | 32篇 |
2003年 | 35篇 |
2002年 | 20篇 |
2001年 | 6篇 |
2000年 | 3篇 |
1999年 | 2篇 |
1998年 | 5篇 |
1997年 | 5篇 |
1996年 | 1篇 |
1995年 | 5篇 |
1994年 | 1篇 |
1993年 | 1篇 |
1992年 | 2篇 |
1991年 | 4篇 |
1990年 | 3篇 |
1989年 | 8篇 |
1988年 | 3篇 |
1987年 | 3篇 |
1986年 | 2篇 |
1985年 | 2篇 |
1983年 | 3篇 |
1982年 | 2篇 |
1981年 | 3篇 |
1979年 | 1篇 |
1977年 | 2篇 |
1973年 | 1篇 |
排序方式: 共有678条查询结果,搜索用时 31 毫秒
101.
Zewen Liu Guangchun Cao† Jian Li Haibo Bao Yongjun Zhang† 《Journal of neurochemistry》2009,110(5):1707-1714
Nicotinic acetylcholine receptors (nAChRs) mediate fast cholinergic synaptic transmission in the insect brain and are targets for neonicotinoid insecticides. Some proteins, other than nAChRs themselves, might play important roles in insect nAChRs function in vivo and in vitro , such as the chaperone, regulator and modulator. Here we report the identification of two nAChR modulators (Nl-lynx1 and Nl-lynx2) in the brown planthopper, Nilaparvata lugens . Analysis of amino acid sequences of Nl-lynx1 and Nl-lynx2 reveals that they are two members of the Ly-6/neurotoxin superfamily, with a cysteine-rich consensus signature motif. Nl-lynx1 and Nl-lynx2 only increased agonist-evoked macroscopic currents of hybrid receptors Nlα1/β2 expressed in Xenopus oocytes, but not change the agonist sensitivity and desensitization properties. For example, Nl-lynx1 increased I max of acetylcholine and imidacloprid to 3.56-fold and 1.72-fold of that of Nlα1/β2 alone, and these folds for Nl-lynx2 were 3.25 and 1.51. When the previously identified Nlα1Y151S mutation was included (Nlα1Y151S /β2), the effects of Nl-lynx1 and Nl-lynx2 on imidacloprid responses, but not acetylcholine response, were different from that in Nlα1/β2. The increased folds in imidacloprid responses by Nl-lynx1 and Nl-lynx2 were much higher in Nlα1Y151S /β2 (3.25-fold and 2.86-fold) than in Nlα1/β2 (1.72-fold and 1.51-fold), which indicated Nl-lynx1 and Nl-lynx2 might also serve as an influencing factor in target-site insensitivity in N. lugens . These findings indicate that nAChRs chaperone, regulator and modulator may be of importance in assessing the likely impact of the target-site mutations such as Y151S upon neonicotinoid insecticide resistance. 相似文献
102.
Chung-Hin Chui Raymond Siu-Ming Wong Roberto Gambari Gregory Yin-Ming Cheng Marcus Chun-Wah Yuen Kit-Wah Chan See-Wai Tong Fung-Yi Lau Paul Bo-San Lai Kim-Hung Lam Cheuk-Lam Ho Chi-Wai Kan Kelvin Sze-Yin Leung Wai-Yeung Wong 《Bioorganic & medicinal chemistry》2009,17(23):7872-7877
A list of diethynylfluorenes and their gold(I) derivatives have been studied for their antitumor activity as a function of their structure–activity relationships. End-capping the fluoren-9-one unit with gold(I) moieties could significantly strengthen the cytotoxic activity in vitro on three human cancer cell lines with induction of reactive oxygen species generation on Hep3B hepatocellular carcinoma cells and exhibit attractive antitumor activity from in vivo nude mice Hep3B xenograft model with limited adverse effects on vital organs including liver and kidney. 相似文献
103.
104.
Thimmaraju Rudrappa Yong Seok Choi Delphis F Levia David R Legates Kelvin H Lee Harsh P Bais 《Plant signaling & behavior》2009,4(6):506-513
Our study organism, Phragmites australis (common reed), is a unique invader in that both native and introduced lineages are found coexisting in North America. This allows one to make direct assessments of physiological differences between these different subspecies and examine how this relates to invasiveness. Recent efforts to understand plant invasive behavior show that some invasive plants secrete a phytotoxin to ward-off encroachment by neighboring plants (allelopathy) and thus provide the invaders with a competitive edge in a given habitat. Here we show that a varying climatic factor like ultraviolet (UV) light leads to photo-degradation of secreted phytotoxin (gallic acid) in P. australis rhizosphere inducing higher mortality of susceptible seedlings. The photo-degraded product of gallic acid (hereafter GA), identified as mesoxalic acid (hereafter MOA), triggered a similar cell death cascade in susceptible seedlings as observed previously with GA. Further, we detected the biological concentrations of MOA in the natural stands of exotic and native P. australis. Our studies also show that the UV degradation of GA is facilitated at an alkaline pH, suggesting that the natural habitat of P. australis may facilitate the photo-degradation of GA. The study highlights the persistence of the photo-degraded phytotoxin in the P. australis''s rhizosphere and its inhibitory effects against the native plants.Key words: ultraviolet, gallic acid, mesoxalic acid, novel weapons, invasive species, Phragmites australis 相似文献
105.
Minhua Zhang Michal Poplawski Kelvin Yen Hui Cheng Erik Bloss Xiao Zhu Harshil Patel Charles V. Mobbs 《PLoS biology》2009,7(11)
How dietary restriction (DR) increases lifespan and decreases disease burden are questions of major interest in biomedical research. Here we report that hypothalamic expression of CREB-binding protein (CBP) and CBP-binding partner Special AT-rich sequence binding protein 1 (SATB-1) is highly correlated with lifespan across five strains of mice, and expression of these genes decreases with age and diabetes in mice. Furthermore, in Caenorhabditis elegans, cbp-1 is induced by bacterial dilution DR (bDR) and the daf-2 mutation, and cbp-1 RNAi specifically in adults completely blocks lifespan extension by three distinct protocols of DR, partially blocks lifespan extension by the daf-2 mutation but not of cold, and blocks delay of other age-related pathologies by bDR. Inhibiting the C. elegans ortholog of SATB-1 and CBP-binding partners daf-16 and hsf-1 also attenuates lifespan extension by bDR, but not other protocols of DR. In a transgenic Aβ42 model of Alzheimer''s disease, cbp-1 RNAi prevents protective effects of bDR and accelerates Aβ42-related pathology. Furthermore, consistent with the function of CBP as a histone acetyltransferase, drugs that enhance histone acetylation increase lifespan and reduce Aβ42-related pathology, protective effects completely blocked by cbp-1 RNAi. Other factors implicated in lifespan extension are also CBP-binding partners, suggesting that CBP constitutes a common factor in the modulation of lifespan and disease burden by DR and the insulin/IGF1 signaling pathway. 相似文献
106.
107.
Chambers RJ Abrams K Castleberry TA Cheng JB Fisher DA Kamath AV Marfat A Nettleton DO Pillar JD Salter ED Sheils AL Shirley JT Turner CR Umland JP Lam KT 《Bioorganic & medicinal chemistry letters》2006,16(3):718-721
Nicotinamide (2) is a potent and selective inhibitor of the PDE4D isozyme and as a chemical tool selectively blocks eosinophil mediator release and chemotaxis thus linking the role of PDE4D to eosinophil function. 相似文献
108.
Kozma K Keusch JJ Hegemann B Luther KB Klein D Hess D Haltiwanger RS Hofsteenge J 《The Journal of biological chemistry》2006,281(48):36742-36751
Thrombospondin type 1 repeats (TSRs) are biologically important domains of extracellular proteins. They are modified with a unique Glcbeta1,3Fucalpha1-O-linked disaccharide on either serine or threonine residues. Here we identify the putative glycosyltransferase, B3GTL, as the beta1,3-glucosyltransferase involved in the biosynthesis of this disaccharide. This enzyme is conserved from Caenorhabditis elegans to man and shares 28% sequence identity with Fringe, the beta1,3-N-acetylglucosaminyltransferase that modifies O-linked fucosyl residues in proteins containing epidermal growth factor-like domains, such as Notch. beta1,3-Glucosyltransferase glucosylates properly folded TSR-fucose but not fucosylated epidermal growth factor-like domain or the non-fucosylated modules. Specifically, the glucose is added in a beta1,3-linkage to the fucose in TSR. The activity profiles of beta1,3-glucosyltransferase and protein O-fucosyltransferase 2, the enzyme that carries out the first step in TSR O-fucosylation, superimpose in endoplasmic reticulum subfractions obtained by density gradient centrifugation. Both enzymes are soluble proteins that efficiently modify properly folded TSR modules. The identification of the beta1,3-glucosyltransferase gene allows us to manipulate the formation of the rare Glcbeta1,3Fucalpha1 structure to investigate its biological function. 相似文献
109.
An X‐linked Myh11‐CreERT2 mouse line resulting from Y to X chromosome‐translocation of the Cre allele 下载免费PDF全文
Fen Wang Yasmin H. Ali Kelvin L. Chan Fei Zou Stefan Offermanns Zhisheng Jiang Zhihua Jiang 《Genesis (New York, N.Y. : 2000)》2017,55(9)
The Myh11‐CreERT2 mouse line (Cre+) has gained increasing application because of its high lineage specificity relative to other Cre drivers targeting smooth muscle cells (SMCs). This Cre allele, however, was initially inserted into the Y chromosome (X/YCre+), which excluded its application in female mice. Our group established a Cre+ colony from male ancestors. Surprisingly, genotype screening identified female carriers that stably transmitted the Cre allele to the following generations. Crossbreeding experiments revealed a pattern of X‐linked inheritance for the transgene (k > 1000), indicating that these female carries acquired the Cre allele through a mechanism of Y to X chromosome translocation. Further characterization demonstrated that in hemizygous X/XCre+ mice Cre activity was restricted to a subset arterial SMCs, with Cre expression in arteries decreased by 50% compared to X/YCre+ mice. This mosaicism, however, diminished in homozygous XCre+/XCre+ mice. In a model of aortic aneurysm induced by a SMC‐specific Tgfbr1 deletion, the homozygous XCre+/XCre+ Cre driver unmasked the aortic phenotype that is otherwise subclinical when driven by the hemizygous X/XCre+ Cre line. In conclusion, the Cre allele carried by this female mouse line is located on the X chromosome and subjected to X‐inactivation. The homozygous XCre+/XCre+ mice produce uniform Cre activity in arterial SMCs. 相似文献
110.
一株产碱性蛋白酶菌株的筛选鉴定及酶学特性研究 总被引:4,自引:0,他引:4
【目的】从丝茅草中筛选得到产蛋白酶菌株并研究驯化过程中微生物群落结构,以及探究该菌株的生长特性和蛋白酶的酶学特性。【方法】通过高通量测序探究来源于丝茅草的菌株在不同培养条件下细菌种类及丰度,通过选择性培养基来筛选能够分解酪素并产生蛋白酶的菌株,通过单因素试验方法确定环境因子对菌株生长和蛋白酶活性的影响。【结果】微生物群落结构在基础培养基和牛肉膏蛋白胨培养基中不同。通过含酪素的选择性培养基里筛选到1株产蛋白酶菌株H-16,经生理生化试验和16S r DNA鉴定知该菌株属于Escherichia marmotae,菌株H-16能产生分子量为70 k Da左右的单亚基蛋白酶。胰蛋白胨、蔗糖、30°C或35°C、p H 7分别为菌株生长的最适氮源、碳源、温度和p H。菌株H-16分泌的蛋白酶最适p H为6–8,在50°C及6%盐度以下酶活性几乎不受影响。此外,Cu(II)和Ag(I)等金属离子能够抑制蛋白酶的活性。【结论】该菌株H-16为嗜中温菌株,能够产生碱性蛋白酶。 相似文献