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91.
Chiara Pesciaroli Francesco Cupini Laura Selbmann Paolo Barghini Massimiliano Fenice 《Polar Biology》2012,35(3):435-445
Fifty-two bacteria were isolated from seawater collected in Kandalaksha Bay, White Sea, Russia, and classified by 16S rDNA
sequencing. Most of the strains belonged to ubiquitous microorganisms. Pseudomonas was the most abundant genus (21 strains), including species of P. fluorescens, P. putida and P. syringae. Serratia was also common (10 strains) with species S. plymuthica and S. proteamaculans. Sphingobacterium, Flavobacterium and Pantoea were less represented (5, 3 and 2 strains, respectively). The only typical bacterium of marine Arctic regions was Shewanella baltica. The strains were tested for their optimal growth temperature in the range 0–45°C. The majority appeared to be psychrotolerant
(42%) or mesophilic-psychrotolerant (40%). In addition, one strain (Bacillus pumilus) showed a rather narrow mesophilic profile. No true psychrophilic bacteria were found. Most of the strains showed a classical
curve with fast growth decrease above the optimum; some others displayed uncommon flat curves with scarce differences between
maximum and minimum of growth in a wide range of temperatures. Moreover, few strains presented an unusual profile being, in
relation to the optimum, more tolerant to high rather than low temperatures. Preferences of the Kandalaksha Bay strains are
generally different from those reported in literature for the same species: optima were at lower temperatures and, sometimes,
ranges were broader showing increased eurythermism. This could indicate adaptation to the wide temperature variations recorded
in this peculiar environment. 相似文献
92.
Avner Schlessinger Matthias B. Wittwer Amber Dahlin Natalia Khuri Massimiliano Bonomi Hao Fan Kathleen M. Giacomini Andrej Sali 《The Journal of biological chemistry》2012,287(45):37745-37756
The solute carrier 6 (SLC6) is a family of ion-dependent transporters that mediate uptake into the cell of osmolytes such as neurotransmitters and amino acids. Four SLC6 members transport GABA, a key neurotransmitter that triggers inhibitory signaling pathways via various receptors (e.g., GABAA). The GABA transporters (GATs) regulate the concentration of GABA available for signaling and are thus targeted by a variety of anticonvulsant and relaxant drugs. Here, we characterize GAT-2, a transporter that plays a role in peripheral GABAergic mechanisms, by constructing comparative structural models based on crystallographic structures of the leucine transporter LeuT. Models of GAT-2 in two different conformations were constructed and experimentally validated, using site-directed mutagenesis. Computational screening of 594,166 compounds including drugs, metabolites, and fragment-like molecules from the ZINC database revealed distinct ligands for the two GAT-2 models. 31 small molecules, including high scoring compounds and molecules chemically related to known and predicted GAT-2 ligands, were experimentally tested in inhibition assays. Twelve ligands were found, six of which were chemically novel (e.g., homotaurine). Our results suggest that GAT-2 is a high selectivity/low affinity transporter that is resistant to inhibition by typical GABAergic inhibitors. Finally, we compared the binding site of GAT-2 with those of other SLC6 members, including the norepinephrine transporter and other GATs, to identify ligand specificity determinants for this family. Our combined approach may be useful for characterizing interactions between small molecules and other membrane proteins, as well as for describing substrate specificities in other protein families. 相似文献
93.
Lopez-Herrera G Tampella G Pan-Hammarström Q Herholz P Trujillo-Vargas CM Phadwal K Simon AK Moutschen M Etzioni A Mory A Srugo I Melamed D Hultenby K Liu C Baronio M Vitali M Philippet P Dideberg V Aghamohammadi A Rezaei N Enright V Du L Salzer U Eibel H Pfeifer D Veelken H Stauss H Lougaris V Plebani A Gertz EM Schäffer AA Hammarström L Grimbacher B 《American journal of human genetics》2012,90(6):986-1001
Most autosomal genetic causes of childhood-onset hypogammaglobulinemia are currently not well understood. Most affected individuals are simplex cases, but both autosomal-dominant and autosomal-recessive inheritance have been described. We performed genetic linkage analysis in consanguineous families affected by hypogammaglobulinemia. Four consanguineous families with childhood-onset humoral immune deficiency and features of autoimmunity shared genotype evidence for a linkage interval on chromosome 4q. Sequencing of positional candidate genes revealed that in each family, affected individuals had a distinct homozygous mutation in LRBA (lipopolysaccharide responsive beige-like anchor protein). All LRBA mutations segregated with the disease because homozygous individuals showed hypogammaglobulinemia and autoimmunity, whereas heterozygous individuals were healthy. These mutations were absent in healthy controls. Individuals with homozygous LRBA mutations had no LRBA, had disturbed B cell development, defective in vitro B cell activation, plasmablast formation, and immunoglobulin secretion, and had low proliferative responses. We conclude that mutations in LRBA cause an immune deficiency characterized by defects in B cell activation and autophagy and by susceptibility to apoptosis, all of which are associated with a clinical phenotype of hypogammaglobulinemia and autoimmunity. 相似文献
94.
Andreazzoli M Gestri G Landi E D'Orsi B Barilari M Iervolino A Vitiello M Wilson SW Dente L 《Biochimie》2012,94(9):2054-2057
We report the identification of a novel partner of Kidins220/ARMS (Kinase D-interacting substrate of 220 kDa/Ankyrin Repeat-rich Membrane Spanning) an adaptor of neurotrophin receptors playing crucial roles during neurogenesis. Screening a phage display library of brain cDNA products we found that D. rerio Pdzrn3, a protein containing RING-finger and PDZ-domains, interacts with Kidins220/ARMS through its first PDZ-domain. Both zebrafish proteins share high homology with the corresponding mammalian proteins and both genes are developmentally expressed in neural districts where early neurogenesis occurs. The interaction was also confirmed by biochemical assays and by co-localization at the tips of growing neurites of PC12 cells induced with nerve growth factor. 相似文献
95.
The objective of the paper is to show the very important biophysical concepts that have been developed with polysaccharides.
In particular, an attempt will be made to relate “a posteriori” the fundamental aspects, both experimental and theoretical,
with some industrial applications of polysaccharide-based materials. The overview of chain conformational aspects includes
relationships between topological features and local dynamics, exemplified for some naturally occurring carbohydrate polymers.
Thus, by using simulation techniques and computational studies, the physicochemical properties of aqueous solutions of polysaccharides
are interpreted. The relevance of conformational disorder–order transitions, chain aggregation, and phase separation to the
underlying role of the ionic contribution to these processes is discussed. We stress the importance of combining information
from analysis of experimental data with that from statistical–thermodynamic models for understanding the conformation, size,
and functional stability of industrially important polysaccharides. The peculiar properties of polysaccharides in industrial
applications are summarized for the particularly important example of nanoparticles production, a field of growing relevance
and scientific interest. 相似文献
96.
Marttila M Lemola E Wallefeld W Memo M Donner K Laing NG Marston S Grönholm M Wallgren-Pettersson C 《The Biochemical journal》2012,442(1):231-239
NM (nemaline myopathy) is a rare genetic muscle disorder defined on the basis of muscle weakness and the presence of structural abnormalities in the muscle fibres, i.e. nemaline bodies. The related disorder cap myopathy is defined by cap-like structures located peripherally in the muscle fibres. Both disorders may be caused by mutations in the TPM2 gene encoding β-Tm (tropomyosin). Tm controls muscle contraction by inhibiting actin-myosin interaction in a calcium-sensitive manner. In the present study, we have investigated the pathogenetic mechanisms underlying five disease-causing mutations in Tm. We show that four of the mutations cause changes in affinity for actin, which may cause muscle weakness in these patients, whereas two show defective Ca2+ activation of contractility. We have also mapped the amino acids altered by the mutation to regions important for actin binding and note that two of the mutations cause altered protein conformation, which could account for impaired actin affinity. 相似文献
97.
Schumacher MA Ye Q Barge MT Zampini M Barillà D Hayes F 《The Journal of biological chemistry》2012,287(31):26146-26154
Segregation of the bacterial multidrug resistance plasmid TP228 requires the centromere-binding protein ParG, the parH centromere, and the Walker box ATPase ParF. The cycling of ParF between ADP- and ATP-bound states drives TP228 partition; ATP binding stimulates ParF polymerization, which is essential for segregation, whereas ADP binding antagonizes polymerization and inhibits DNA partition. The molecular mechanism involved in this adenine nucleotide switch is unclear. Moreover, it is unknown how any Walker box protein polymerizes in an ATP-dependent manner. Here, we describe multiple ParF structures in ADP- and phosphomethylphosphonic acid adenylate ester (AMPPCP)-bound states. ParF-ADP is monomeric but dimerizes when complexed with AMPPCP. Strikingly, in ParF-AMPPCP structures, the dimers interact to create dimer-of-dimer "units" that generate a specific linear filament. Mutation of interface residues prevents both polymerization and DNA segregation in vivo. Thus, these data provide insight into a unique mechanism by which a Walker box protein forms polymers that involves the generation of ATP-induced dimer-of-dimer building blocks. 相似文献
98.
99.
Piepoli A Tavano F Copetti M Mazza T Palumbo O Panza A di Mola FF Pazienza V Mazzoccoli G Biscaglia G Gentile A Mastrodonato N Carella M Pellegrini F di Sebastiano P Andriulli A 《PloS one》2012,7(3):e33663
Background and Aim
Altered expression of microRNAs (miRNAs) hallmarks many cancer types. The study of the associations of miRNA expression profile and cancer phenotype could help identify the links between deregulation of miRNA expression and oncogenic pathways.Methods
Expression profiling of 866 human miRNAs in 19 colorectal and 17 pancreatic cancers and in matched adjacent normal tissues was investigated. Classical paired t-test and random forest analyses were applied to identify miRNAs associated with tissue-specific tumors. Network analysis based on a computational approach to mine associations between cancer types and miRNAs was performed.Results
The merge between the two statistical methods used to intersect the miRNAs differentially expressed in colon and pancreatic cancers allowed the identification of cancer-specific miRNA alterations. By miRNA-network analysis, tissue-specific patterns of miRNA deregulation were traced: the driving miRNAs were miR-195, miR-1280, miR-140-3p and miR-1246 in colorectal tumors, and miR-103, miR-23a and miR-15b in pancreatic cancers.Conclusion
MiRNA expression profiles may identify cancer-specific signatures and potentially useful biomarkers for the diagnosis of tissue specific cancers. miRNA-network analysis help identify altered miRNA regulatory networks that could play a role in tumor pathogenesis. 相似文献100.
Giovanni Minardi Giordano Zampi Amedeo Pergolini Giovanni Pulignano Massimiliano Scappaticci Francesca Moschella Orsini Gaetano Pero Paola Lilla Della Monica Giovanni Cioffi Francesco Musumeci 《Cardiovascular ultrasound》2012,10(1):1-7