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31.
The early adaptive evolution of calmodulin 总被引:7,自引:0,他引:7
Baba ML; Goodman M; Berger-Cohn J; Demaille JG; Matsuda G 《Molecular biology and evolution》1984,1(6):442-455
Interaction between gene duplication and natural selection in molecular
evolution was investigated utilizing a phylogenetic tree constructed by the
parsimony procedure from amino acid sequences of 50 calmodulin- family
protein members. The 50 sequences, belonging to seven protein lineages
related by gene duplication (calmodulin itself, troponin-C, alkali and
regulatory light chains of myosin, parvalbumin, intestinal calcium-binding
protein, and glial S-100 phenylalanine-rich protein), came from a wide
range of eukaryotic taxa and yielded a denser tree (more branch points
within each lineage) than in earlier studies. Evidence obtained from the
reconstructed pattern of base substitutions and deletions in these
ancestral loci suggests that, during the early history of the family,
selection acted as a transforming force on expressed genes among the
duplicates to encode molecular sites with new or modified functions. In
later stages of descent, however, selection was a conserving force that
preserved the structures of many coadapted functional sites. Each branch of
the family was found to have a unique average tempo of evolutionary change,
apparently regulated through functional constraints. Proteins whose
functions dictate multiple interaction with several other macromolecules
evolved more slowly than those which display fewer protein-protein and
protein-ion interactions, e.g., calmodulin and next troponin-C evolved at
the slowest average rates, whereas parvalbumin evolved at the fastest. The
history of all lineages, however, appears to be characterized by rapid
rates of evolutionary change in earlier periods, followed by slower rates
in more recent periods. A particularly sharp contrast between such fast and
slow rates is found in the evolution of calmodulin, whose rate of change in
earlier eukaryotes was manyfold faster than the average rate over the past
1 billion years. In fact, the amino acid replacements in the nascent
calmodulin lineage occurred at residue positions that in extant metazoans
are largely invariable, lending further support to the Darwinian hypothesis
that natural selection is both a creative and a conserving force in
molecular evolution.
相似文献
32.
Petra Leidinger Christina Backes Stephanie Deutscher Katja Schmitt Sabine C Mueller Karen Frese Jan Haas Klemens Ruprecht Friedemann Paul Cord St?hler Christoph JG Lang Benjamin Meder Tamas Bartfai Eckart Meese Andreas Keller 《Genome biology》2013,14(7):R78
Background
Alzheimer disease (AD) is the most common form of dementia but the identification of reliable, early and non-invasive biomarkers remains a major challenge. We present a novel miRNA-based signature for detecting AD from blood samples.Results
We apply next-generation sequencing to miRNAs from blood samples of 48 AD patients and 22 unaffected controls, yielding a total of 140 unique mature miRNAs with significantly changed expression levels. Of these, 82 have higher and 58 have lower abundance in AD patient samples. We selected a panel of 12 miRNAs for an RT-qPCR analysis on a larger cohort of 202 samples, comprising not only AD patients and healthy controls but also patients with other CNS illnesses. These included mild cognitive impairment, which is assumed to represent a transitional period before the development of AD, as well as multiple sclerosis, Parkinson disease, major depression, bipolar disorder and schizophrenia. miRNA target enrichment analysis of the selected 12 miRNAs indicates an involvement of miRNAs in nervous system development, neuron projection, neuron projection development and neuron projection morphogenesis. Using this 12-miRNA signature, we differentiate between AD and controls with an accuracy of 93%, a specificity of 95% and a sensitivity of 92%. The differentiation of AD from other neurological diseases is possible with accuracies between 74% and 78%. The differentiation of the other CNS disorders from controls yields even higher accuracies.Conclusions
The data indicate that deregulated miRNAs in blood might be used as biomarkers in the diagnosis of AD or other neurological diseases. 相似文献33.
34.
C André Lévesque Henk Brouwer Liliana Cano John P Hamilton Carson Holt Edgar Huitema Sylvain Raffaele Gregg P Robideau Marco Thines Joe Win Marcelo M Zerillo Gordon W Beakes Jeffrey L Boore Dana Busam Bernard Dumas Steve Ferriera Susan I Fuerstenberg Claire MM Gachon Elodie Gaulin Francine Govers Laura Grenville-Briggs Neil Horner Jessica Hostetler Rays HY Jiang Justin Johnson Theerapong Krajaejun Haining Lin Harold JG Meijer Barry Moore Paul Morris Vipaporn Phuntmart Daniela Puiu Jyoti Shetty Jason E Stajich Sucheta Tripathy Stephan Wawra Pieter van West Brett R Whitty Pedro M Coutinho Bernard Henrissat Frank Martin Paul D Thomas Brett M Tyler Ronald P De Vries Sophien Kamoun Mark Yandell Ned Tisserat C Robin Buell 《Genome biology》2010,11(7):1-22
35.
Espinoza-Fonseca LM Trujillo-Ferrara JG 《Bioorganic & medicinal chemistry letters》2006,16(5):1217-1220
Fully flexible docking of KT5720, an allosteric modulator of the muscarinic receptors, was performed on a dynamic model of the M(1) muscarinic acetylcholine receptor. The results confirmed the existence of a second allosteric site, located on the intracellular face of the receptor. These results would be beneficial for the design of modulators of this receptor to be used as an effective alternative against the Alzheimer's disease. 相似文献
36.
Marvin A. Soriano-Ursúa José G. Trujillo-Ferrara José Correa-Basurto 《Journal of molecular modeling》2009,15(10):1203-1211
The trachea of a guinea pig is widely used in drug development assays focused on the treatment of pulmonary diseases. Some
of these drugs relax the airways by binding to the guinea pig β2-adrenoceptor (Gβ2AR). In this work, the amino acid sequence of the Gβ2AR was searched to carry out homology modeling, using the Swiss-Model server, with the human β2AR as the parent template. The Gβ2AR 3-D structure was structurally and energetically optimized in vacuo using NAMD 2.6 program. The refined 3-D model obtained was used for further study. Molecular docking simulations were performed
by testing a set of well-known β2AR ligands using the AutoDock 3.0.5 program. The results show that the homology model of Gβ2AR has a 3-D structure very similar to the crystal structure of recently studied human β2AR. This was also corroborated by identity (94.23%), Ramachandran map, and docking results. The theoretical simulation showed
that the ligands bind at sites that are similar to those reported for the human β2AR. The R-enantiomer ligands showed correlation with in vitro data. We have obtained a Gβ2AR 3-D model which can be used to carry out computational screening as a complementary tool during the drug design and experimental
tests under guinea pig models. 相似文献
37.
38.
Marvin A. Soriano-Ursúa José Correa-Basurto Ignacio Valencia-Hernández Marcos A. Amezcua-Gutiérrez Itzia I. Padilla-Martínez José G. Trujillo-Ferrara 《Bioorganic & medicinal chemistry letters》2010,20(19):5623-5629
We tested a set of boron containing arylethanolamine derivatives on the human and guinea pig β2 adrenoceptor (β2AR) 3-D structures by docking methodology. The compound with the highest affinity based on docking analysis, (R)-4-(2-(tert-butylamino)-1-hydroxyethyl)-2-(hydroxymethyl)phenyl hydrogen phenylboronate (boronterol) was synthesized, characterized and tested in guinea pig tracheal rings at basal tone and with histamine-induced contractions. Boronterol was at least eightfold more potent than salbutamol as a smooth muscle relaxant drug (judged by the EC50 values) and showed a similar maximal relaxant effect as isoproterenol. ICI118,551 showed competitive antagonism on the relaxing effect of boronterol. These results suggest the β2AR agonist action of boronterol. 相似文献
39.
40.
Soriano-Ursúa MA Correa-Basurto J Trujillo-Ferrara JG Kaumann AJ 《Journal of molecular modeling》2011,17(10):2525-2538
The affinity of the classical β2 adrenoceptor-selective inverse agonist ICI118,551 is notoriously lower for porcine β2 adrenoceptors (p2βAR) than for human β2 adrenoceptors (hβ2AR) but molecular mechanisms for this difference are still unclear. Homology 3-D models of pβ2AR can be useful in predicting similarities and differences, which might in turn increase the comparative understanding of
ligand interactions with the hβ2AR. In this work, the pβ2AR amino acid sequence was used to carry out homology modeling. The selected pβ2AR 3-D structure was structurally and energetically optimized and used as a model for further theoretical study. The homology
model of pβ2AR has a 3-D structure very similar to the crystal structures of recently studied hβ2AR. This was also corroborated by sequence identity, RMSD, Ramachandran map, TM-score and docking results. Upon performing molecular docking simulations with the AutoDock4.0.1 program on pβ2AR, it was found that a set of well-known β2AR ligands reach two distinct binding sites on pβ2AR. Whereas one of these sites is similar to that reported on the hβ2AR crystal structure, the other can explain some important experimental observations. Additionally, the theoretical affinity
estimated for ICI118,551 closely agrees with affinities estimated from experimental in vitro data. The experimental differences
between the human/porcine β2ARs in relation to ligand affinity can in part be elucidated by observations in this molecular modeling study. 相似文献