全文获取类型
收费全文 | 295篇 |
免费 | 27篇 |
出版年
2023年 | 1篇 |
2022年 | 4篇 |
2021年 | 8篇 |
2020年 | 3篇 |
2019年 | 5篇 |
2018年 | 10篇 |
2017年 | 8篇 |
2016年 | 11篇 |
2015年 | 18篇 |
2014年 | 19篇 |
2013年 | 16篇 |
2012年 | 26篇 |
2011年 | 28篇 |
2010年 | 15篇 |
2009年 | 9篇 |
2008年 | 22篇 |
2007年 | 13篇 |
2006年 | 17篇 |
2005年 | 18篇 |
2004年 | 15篇 |
2003年 | 23篇 |
2002年 | 21篇 |
2000年 | 1篇 |
1999年 | 1篇 |
1998年 | 1篇 |
1997年 | 2篇 |
1996年 | 2篇 |
1994年 | 2篇 |
1989年 | 1篇 |
1985年 | 1篇 |
1982年 | 1篇 |
排序方式: 共有322条查询结果,搜索用时 46 毫秒
21.
The uptake of glutamate in nerve synapses is carried out by the excitatory amino acid transporters (EAATs), involving the cotransport of a proton and three Na+ ions and the countertransport of a K+ ion. In this study, we use an EAAT3 homology model to calculate the pKa of several titratable residues around the glutamate binding site to locate the proton carrier site involved in the translocation of the substrate. After identifying E374 as the main candidate for carrying the proton, we calculate the protonation state of this residue in different conformations of EAAT3 and with different ligands bound. We find that E374 is protonated in the fully bound state, but removing the Na2 ion and the substrate reduces the pKa of this residue and favors the release of the proton to solution. Removing the remaining Na+ ions again favors the protonation of E374 in both the outward- and inward-facing states, hence the proton is not released in the empty transporter. By calculating the pKa of E374 with a K+ ion bound in three possible sites, we show that binding of the K+ ion is necessary for the release of the proton in the inward-facing state. This suggests a mechanism in which a K+ ion replaces one of the ligands bound to the transporter, which may explain the faster transport rates of the EAATs compared to its archaeal homologs. 相似文献
22.
Sandra Lightle Serdar Aykent Nathan Lacher Vesselin Mitaksov Kristine Wells James Zobel Theodore Oliphant 《Protein science : a publication of the Protein Society》2010,19(4):753-762
Human IgG2 antibodies may exist in at least three distinct structural isomers due to disulfide shuffling within the upper hinge region. Antibody interactions with Fc gamma receptors and the complement component C1q contribute to immune effector functions. These interactions could be impacted by the accessibility and structure of the hinge region. To examine the role structural isomers may have on effector functions, a series of cysteine to serine mutations were made on a human IgG2 backbone. We observed structural homogeneity with these mutants and mapped the locations of their disulfide bonds. Importantly, there was no observed difference in binding to any of the Fc gamma receptors or C1q between the mutants and the wild‐type IgG2. However, differences were seen in the apparent binding affinity of these antibodies that were dependent on the selection of the secondary detection antibody used. 相似文献
23.
Yuri Kotliarov Serdar Bozdag Hangjiong Cheng Stefan Wuchty Jean-Claude Zenklusen Howard A Fine 《BMC medical genomics》2010,3(1):1-5
Background
Genomic copy number alterations are widely associated with a broad range of human tumors and offer the potential to be used as a diagnostic tool. Especially in the emerging era of personalized medicine medical informatics tools that allow the fast visualization and analysis of genomic alterations of a patient's genomic profile for diagnostic and potential treatment purposes increasingly gain importance.Results
We developed CNAReporter, a software tool that allows users to visualize SNP-specific data obtained from Affymetrix arrays and generate PDF-reports as output. We combined standard algorithms for the analysis of chromosomal alterations, utilizing the widely applied GenePattern framework. As an example, we show genome analyses of two patients with distinctly different CNA profiles using the tool.Conclusions
Glioma subtypes, characterized by different genomic alterations, are often treated differently but can be difficult to differentiate pathologically. CNAReporter offers a user-friendly way to visualize and analyse genomic changes of any given tumor genomic profile, thereby leading to an accurate diagnosis and patient-specific treatment. 相似文献24.
25.
26.
27.
T. Amanda Strom Serdar Durdagi Suha Salih Ersoz Ramin Ekhteiari Salmas Claudiu T. Supuran Andrew R. Barron 《Journal of peptide science》2015,21(12):862-870
A series of Fmoc‐Phe(4‐aza‐C60)‐OH of fullerene amino acid derived peptides have been prepared by solid phase peptide synthesis, in which the terminal amino acid, Phe(4‐aza‐C60)‐OH, is derived from the dipolar addition to C60 of the Fmoc‐Nα‐protected azido amino acids derived from phenylalanine: Fmoc‐Phe(4‐aza‐C60)‐Lys3‐OH ( 1 ), Fmoc‐Phe(4‐aza‐C60)‐Pro‐Hyp‐Lys‐OH ( 2 ), and Fmoc‐Phe(4‐aza‐C60)‐Hyp‐Hyp‐Lys‐OH ( 3 ). The inhibition constant of our fullerene aspartic protease PRIs utilized FRET‐based assay to evaluate the enzyme kinetics of HIV‐1 PR at various concentrations of inhibitors. Simulation of the docking of the peptide Fmoc‐Phe‐Pro‐Hyp‐Lys‐OH overestimated the inhibition, while the amino acid PRIs were well estimated. The experimental results show that C60‐based amino acids are a good base structure in the design of protease inhibitors and that their inhibition can be improved upon by the addition of designer peptide sequences. Copyright © 2015 European Peptide Society and John Wiley & Sons, Ltd. 相似文献
28.
Sam S Kucukasik F Yenigun O Nicolaus B Oner ET Yukselen MA 《Bioresource technology》2011,102(2):1788-1794
This study reports the first systematic investigation of the flocculation dynamics of exopolysaccharides (EPSs) produced by a halophilic bacterial strain grown on pretreated molasses as fermentation substrate. The potential use of these EPSs as an easily biodegradable, natural alternative for synthetic polyelectrolytes which are widely used and contain toxic and carcinogenic monomers was investigated. Flocculating activities of the EPS samples in synthetic water, synthetic sea water and natural sea water media which were used as model raw waters were monitored via the Photometric Dispersion Analyser (PDA 2000) instrument and removals were determined by measuring residual turbidities. One of the six EPS specimens, which formed the largest flocs thus performed highest turbidity removal, exhibited flocculation performance and particle removal efficiency comparable with commercial cationic, nonionic and anionic synthetic polyelectrolytes. 相似文献
29.
Durdagi S Şentürk M Ekinci D Balaydın HT Göksu S Küfrevioğlu Öİ Innocenti A Scozzafava A Supuran CT 《Bioorganic & medicinal chemistry》2011,19(4):1381-1389
Carbonic anhydrases (CAs, EC 4.2.1.1) are inhibited by sulfonamides, inorganic anions, phenols, coumarins (acting as prodrugs) and polyamines. A novel class of CA inhibitors (CAIs), interacting with the CA isozymes I, II (cytosolic) and IX, XII (transmembrane, tumor-associated) in a different manner, is reported here. Kinetic measurements allowed us to identify hydroxy-/methoxy-substituted benzoic acids as well as di-/tri-methoxy benzenes as submicromolar-low micromolar inhibitors of the four CA isozymes. Molecular docking studies of a set of such inhibitors within CA I and II allowed us to understand the inhibition mechanism. This new class of inhibitors binds differently compared to all other classes of inhibitors known to date: they were found between the phenol-binding site and the coumarin-binding site, filling thus the middle of the enzyme cavity. They exploit different interactions with amino acid residues and water molecules from the CA active site compared to other classes of inhibitors, offering the possibility to design CAIs with an interesting inhibition profile compared to the clinically used sulfonamides/sulfamates. 相似文献
30.
Serdar Oztora Osman Korkmaz Nezih Dagdeviren Yahya Celik Ayse Caylan Mehmet S Top Talip Asil 《BMC neurology》2011,11(1):103