首页 | 本学科首页   官方微博 | 高级检索  
文章检索
  按 检索   检索词:      
出版年份:   被引次数:   他引次数: 提示:输入*表示无穷大
  收费全文   398篇
  免费   24篇
  2024年   2篇
  2023年   9篇
  2022年   6篇
  2021年   21篇
  2020年   7篇
  2019年   14篇
  2018年   18篇
  2017年   12篇
  2016年   19篇
  2015年   30篇
  2014年   38篇
  2013年   31篇
  2012年   37篇
  2011年   38篇
  2010年   21篇
  2009年   14篇
  2008年   24篇
  2007年   15篇
  2006年   12篇
  2005年   14篇
  2004年   13篇
  2003年   13篇
  2002年   4篇
  2001年   2篇
  2000年   1篇
  1999年   1篇
  1998年   1篇
  1997年   4篇
  1989年   1篇
排序方式: 共有422条查询结果,搜索用时 15 毫秒
81.
Stability of microbial communities can impact the ability of dispersed cells to colonize a new habitat. Saturated brines and their halophile communities are presumed to be steady state systems due to limited environmental perturbations. In this study, the bacteriorhodopsin-containing fraction of the haloarchaeal community from Eilat salt crystallizer ponds was sampled five times over 3 years. Analyses revealed the existence of a constant core as several OTUs were found repeatedly over the length of the study: OTUs comprising 52 % of the total cloned and sequenced PCR amplicons were found in every sample, and OTUs comprising 89 % of the total sequences were found in more than one, and often more than two samples. LIBSHUFF and UNIFRAC analyses showed statistical similarity between samples and Spearman’s coefficient denoted significant correlations between OTU pairs, indicating non-random patterns in abundance and co-occurrence of detected OTUs. Further, changes in the detected OTUs were statistically linked to deviations in salinity. We interpret these results as indicating the existence of an ever-present core bacteriorhodopsin-containing Eilat crystallizer community that fluctuates in population densities, which are controlled by salinity rather than the extinction of some OTUs and their replacement through immigration and colonization.  相似文献   
82.
83.
Cathelicidins such as the human 37-amino acid peptide (LL-37) are peptides that not only potently kill microbes but also trigger inflammation by enabling immune recognition of endogenous nucleic acids. Here, a detailed structure–function analysis of LL-37 was performed to understand the details of this process. Alanine scanning of 34-amino acid peptide (LL-34) showed that some variants displayed increased antimicrobial activity against Staphylococcus aureus and group A Streptococcus. In contrast, different substitutions clustered on the hydrophobic face of the LL-34 alpha helix inhibited the ability of those variants to promote type 1 interferon expression in response to U1 RNA or to present U1 to the scavenger receptor (SR) B1 on the keratinocyte cell surface. Small-angle X-ray scattering experiments of the LL-34 variants LL-34, F5A, I24A, and L31A demonstrated that these peptides form cognate supramolecular structures with U1 characterized by inter-dsRNA spacings of approximately 3.5 nm, a range that has been previously shown to activate toll-like receptor 3 by the parent peptide LL-37. Therefore, while alanine substitutions on the hydrophobic face of LL-34 led to loss of binding to SRs and the complete loss of autoinflammatory responses in epithelial and endothelial cells, they did not inhibit the ability to organize with U1 RNA in solution to associate with toll-like receptor 3. These observations advance our understanding of how cathelicidin mediates the process of innate immune self-recognition to enable inert nucleic acids to trigger inflammation. We introduce the term “innate immune vetting” to describe the capacity of peptides such as LL-37 to enable certain nucleic acids to become an inflammatory stimulus through SR binding prior to cell internalization.  相似文献   
84.
85.
Free iron typically leads to the formation of excess free radicals, and additional iron deposition in the liver contributes to the oxidative pathologic processes of liver disease. Many pharmacological properties of the insectivorous plant Drosera burmannii Vahl. have been reported in previous studies; however, there is no evidence of its antioxidant or hepatoprotective potential against iron overload. The antioxidant activity of 70% methanolic extract of D. burmannii (DBME) was evaluated. DBME showed excellent DPPH, hydroxyl, hypochlorous, superoxide, singlet oxygen, nitric oxide, peroxynitrite radical and hydrogen peroxide scavenging activity. A substantial iron chelation (IC50 = 40.90 ± 0.31 μg/ml) and supercoiled DNA protection ([P]50 = 50.41 ± 0.55 μg) were observed. DBME also displayed excellent in vivo hepatoprotective activity in iron-overloaded Swiss albino mice compared to the standard desirox treatment. Administration of DBME significantly normalized serum enzyme levels and restored liver antioxidant enzymes levels. DBME lowered the raised levels of liver damage parameters, also reflected from the morphological analysis of the liver sections. DBME also reduced liver iron content by 115.90% which is also seen by Perls’ staining. A phytochemical analysis of DBME confirms the presence of various phytoconstituents, including phenols, flavonoids, carbohydrates, tannins, alkaloids and ascorbic acid. Alkaloids, phenols and flavonoids were abundantly found in DBME. An HPLC analysis of DBME revealed the presence of purpurin, catechin, tannic acid, reserpine, methyl gallate and rutin. Purpurin, tannic acid, methyl gallate and rutin displayed excellent iron chelation but exhibited cytotoxicity toward normal (WI-38) cells; while DBME found to be non-toxic to the normal cells. These findings suggest that the constituents present in DBME contributed to its iron chelation activity. Additional studies are needed to determine if DBME can be used as a treatment for iron overload diseases.  相似文献   
86.
Striatal dopamine D2 receptor (D2R) relies upon G protein- and β-arrestin-dependent signaling pathways to convey its action on motor control and behavior. Considering that D2R activation inhibits Akt in the striatum and that huntingtin physiological functions are affected by Akt phosphorylation, we sought to investigate whether D2R-mediated signaling could regulate huntingtin phosphorylation. We demonstrate that D2R activation decreases huntingtin phosphorylation on its Akt site. This dephosphorylation event depends upon the Gαi-dependent engagement of specific members of the protein phosphatase metallo-dependent (PPM/PP2C) family and is independent of β-arrestin 2. These observations identify the PPM/PP2C family as a mediator of G protein-coupled receptor signaling and thereby suggest a novel mechanism of dopaminergic signaling.  相似文献   
87.
88.
89.
Cationic trialkylammonium‐substituted α‐, β‐, and γ‐cyclodextrins containing trimethyl‐, triethyl‐, and tri‐n‐propylammonium substituent groups were synthesized and analyzed for utility as water‐soluble chiral nuclear magnetic resonance (NMR) solvating agents. Racemic and enantiomerically pure (3‐chloro‐2‐hydroxypropyl)trimethyl‐, triethyl‐, and tri‐n‐propyl ammonium chloride were synthesized from the corresponding trialkyl amine hydrochloride and either racemic or enantiomerically pure epichlorohydrin. The ammonium salts were then reacted with α‐, β‐, and γ‐cyclodextrins at basic pH to provide the corresponding randomly substituted cationic cyclodextrins. The 1H NMR spectra of a range of anionic, aromatic compounds was recorded with the cationic cyclodextrins. Cyclodextrins with a single stereochemistry at the hydroxy group on the (2‐hydroxypropyl)trialkylammonium chloride substituent were often but not always more effective than the corresponding cyclodextrin in which the C‐2 position was racemic. In several cases, the larger triethyl or tri‐n‐propyl derivatives were more effective than the corresponding trimethyl derivative at causing enantiomeric differentiation. None of the cyclodextrin derivatives were consistently the most effective for all of the anionic compounds studied. Chirality 28:299–305, 2016. © 2016 Wiley Periodicals, Inc.  相似文献   
90.
The role of circadian clocks in timing daily behaviors is widely acknowledged, and while empirical evidence suggests that clock period is correlated with the preferred phase of a rhythmic behavior (chronotype), other clock properties have also been hypothesized to underlie chronotype variation. Here, we report that fruit fly Drosophila melanogaster populations exhibiting evening emergence chronotype (late) are characterized by higher incidence of behavioral arrhythmicity in constant dim light, wider range of entrainment, reduced rates of re-entrainment to simulated jet-lag and higher amplitude of both entrained and free-running rhythms as compared to those exhibiting morning emergence chronotype (early). Our results thus highlight the role of circadian clock properties such as zeitgeber sensitivity, amplitude and coupling in driving chronotype variation.  相似文献   
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号