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排序方式: 共有482条查询结果,搜索用时 15 毫秒
41.
Carvalho AM Freitas AT Oliveira AL Sagot MF 《IEEE/ACM transactions on computational biology and bioinformatics / IEEE, ACM》2006,3(2):126-140
We propose a new algorithm for identifying cis-regulatory modules in genomic sequences. The proposed algorithm, named RISO, uses a new data structure, called box-link, to store the information about conserved regions that occur in a well-ordered and regularly spaced manner in the data set sequences. This type of conserved regions, called structured motifs, is extremely relevant in the research of gene regulatory mechanisms since it can effectively represent promoter models. The complexity analysis shows a time and space gain over the best known exact algorithms that is exponential in the spacings between binding sites. A full implementation of the algorithm was developed and made available online. Experimental results show that the algorithm is much faster than existing ones, sometimes by more than four orders of magnitude. The application of the method to biological data sets shows its ability to extract relevant consensi. 相似文献
42.
Marie-France Langelier Donald D. Ruhl Jamie L. Planck W. Lee Kraus John M. Pascal 《The Journal of biological chemistry》2010,285(24):18877-18887
43.
44.
Houliston RS Endtz HP Yuki N Li J Jarrell HC Koga M van Belkum A Karwaski MF Wakarchuk WW Gilbert M 《The Journal of biological chemistry》2006,281(17):11480-11486
We have identified a sialate O-acetyltransferase in the lipo-oligosaccharide biosynthesis locus of Campylobacter jejuni. Strains possessing this locus are known to produce sialylated outer core structures that mimic host gangliosides, and have been implicated in triggering the onset of Guillain-Barré syndrome. The acetyltransferase, which was cloned and expressed as a fusion construct in Escherichia coli, is soluble and homologous with members of the NodL-LacA-CysE family of O-acetyltransferases. This enzyme catalyzes the transfer of O-acetyl groups onto oligosaccharide-bound sialic acid, with a high specificity for terminal alpha2,8-linked residues. The modification is directed to C-9 and not C-7 as is believed to occur more commonly in other organisms. Despite their wide prevalence and importance in both eukaryotes and prokaryotes, this is the first report to describe the characterization of a purified sialate O-acetyltransferase. 相似文献
45.
Helfer E Nevalainen EM Naumanen P Romero S Didry D Pantaloni D Lappalainen P Carlier MF 《The EMBO journal》2006,25(6):1184-1195
Twinfilins are conserved actin-binding proteins composed of two actin depolymerizing factor homology (ADF-H) domains. Twinfilins are involved in diverse morphological and motile processes, but their mechanism of action has not been elucidated. Here, we show that mammalian twinfilin both sequesters ADP-G-actin and caps filament barbed ends with preferential affinity for ADP-bound ends. Twinfilin replaces capping protein and promotes motility of N-WASP functionalized beads in a biomimetic motility assay, indicating that the capping activity supports twinfilin's function in motility. Consistently, in vivo twinfilin localizes to actin tails of propelling endosomes. The ADP-actin-sequestering activity cooperates with the filament capping activity of twinfilin to finely regulate motility due to processive filament assembly catalyzed by formin-functionalized beads. The isolated ADF-H domains do not cap barbed ends nor promote motility, but sequester ADP-actin, the C-terminal domain showing the highest affinity. A structural model for binding of twinfilin to barbed ends is proposed based on the similar foldings of twinfilin ADF-H domains and gelsolin segments. 相似文献
46.
In this study, a cleavable signal peptide fused to the enhanced green fluorescent protein (EGFP) was tagged to the extracellular
N-terminus of the human dopamine D2 receptor short and long isoforms (D2S and D2L). Ligand-binding properties of EGFP-tagged
receptors were essentially unchanged in comparison to their respective wild-type receptors. The dopamine-mediated activation
of both EGFP-D2 isoforms generated a robust inhibition of adenylyl cyclase type 5 in intact cells. In addition, the receptor
density of EGFP-D2S and EGFP-D2L in transfected human embryonic kidney 293 (HEK293) cells was not altered when compared to
cells transfected with the untagged D2S and D2L. However, the receptor densities of untagged and EGFP-tagged D2L were significantly
lower in comparison to those measured with D2S constructs. Moreover, the receptor density of EGFP-D2S and EGFP-D2L was differentially
upregulated in cells treated with antipsychotic drugs. As assessed by confocal microscopy, both EGFP-D2 isoforms were present
on the cell surface. Notably, in contrast to the predominant plasma membrane localization of EGFP-D2S, EGFP-D2L was visualized
both on the plasma membrane and intracellularly before dopamine exposure. Importantly, EGFP-D2S and EGFP-D2L are robustly
internalized after dopamine treatment. Overall, our data suggest a differential intracellular sorting of D2S and D2L. 相似文献
47.
Blankenfeldt W Kerr ID Giraud MF McMiken HJ Leonard G Whitfield C Messner P Graninger M Naismith JH 《Structure (London, England : 1993)》2002,10(6):773-786
dTDP-6-deoxy-L-lyxo-4-hexulose reductase (RmlD) catalyzes the final step in the conversion of dTDP-D-glucose to dTDP-L-rhamnose in an NAD(P)H- and Mg2+-dependent reaction. L-rhamnose biosynthesis is an antibacterial target. The structure of RmlD from Salmonella enterica serovar Typhimurium has been determined, and complexes with NADH, NADPH, and dTDP-L-rhamnose are reported. RmlD differs from other short chain dehydrogenases in that it has a novel dimer interface that contains Mg2+. Enzyme catalysis involves hydride transfer from the nicotinamide ring of the cofactor to the C4'-carbonyl group of the substrate. The substrate is activated through protonation by a conserved tyrosine. NAD(P)H is bound in a solvent-exposed cleft, allowing facile replacement. We suggest a novel role for the conserved serine/threonine residue of the catalytic triad of SDR enzymes. 相似文献
48.
Hébert L Moumen B Pons N Duquesne F Breuil MF Goux D Batto JM Laugier C Renault P Petry S 《PloS one》2012,7(1):e29953
The Taylorella genus comprises two species: Taylorella equigenitalis, which causes contagious equine metritis, and Taylorella asinigenitalis, a closely-related species mainly found in donkeys. We herein report on the first genome sequence of T. asinigenitalis, analyzing and comparing it with the recently-sequenced T. equigenitalis genome. The T. asinigenitalis genome contains a single circular chromosome of 1,638,559 bp with a 38.3% GC content and 1,534 coding sequences (CDS). While 212 CDSs were T. asinigenitalis-specific, 1,322 had orthologs in T. equigenitalis. Two hundred and thirty-four T. equigenitalis CDSs had no orthologs in T. asinigenitalis. Analysis of the basic nutrition metabolism of both Taylorella species showed that malate, glutamate and alpha-ketoglutarate may be their main carbon and energy sources. For both species, we identified four different secretion systems and several proteins potentially involved in binding and colonization of host cells, suggesting a strong potential for interaction with their host. T. equigenitalis seems better-equipped than T. asinigenitalis in terms of virulence since we identified numerous proteins potentially involved in pathogenicity, including hemagluttinin-related proteins, a type IV secretion system, TonB-dependent lactoferrin and transferrin receptors, and YadA and Hep_Hag domains containing proteins. This is the first molecular characterization of Taylorella genus members, and the first molecular identification of factors potentially involved in T. asinigenitalis and T. equigenitalis pathogenicity and host colonization. This study facilitates a genetic understanding of growth phenotypes, animal host preference and pathogenic capacity, paving the way for future functional investigations into this largely unknown genus. 相似文献
49.
Giraud MF Paumard P Sanchez C Brèthes D Velours J Dautant A 《Journal of structural biology》2012,177(2):490-497
The F1FO-ATP synthase is a rotary molecular nanomotor. F1 is a chemical motor driven by ATP hydrolysis while FO is an electrical motor driven by the proton flow. The two stepping motors are mechanically coupled through a common rotary shaft. Up to now, the three available crystal structures of the F1c10 sub-complex of the yeast F1FO-ATP synthase were isomorphous and then named yF1c10(I). In this crystal form, significant interactions of the c10-ring with the F1-head of neighboring molecules affected the overall conformation of the F1-c-ring complex. The symmetry axis of the F1-head and the inertia axis of the c-ring were tilted near the interface between the F1-central stalk and the c-ring rotor, resulting in an unbalanced machine. We have solved a new crystal form of the F1c10 complex, named yF1c10(II), inhibited by adenylyl-imidodiphosphate (AMP-PNP) and dicyclohexylcarbodiimide (DCCD), at 6.5 Å resolution in which the crystal packing has a weaker influence over the conformation of the F1-c-ring complex. yF1c10(II) provides a model of a more efficient generator. yF1c10(II) and bovine bF1c8 structures share a common rotor architecture with the inertia center of the F1-stator close to the rotor axis. 相似文献
50.
Dastani Z Hivert MF Timpson N Perry JR Yuan X Scott RA Henneman P Heid IM Kizer JR Lyytikäinen LP Fuchsberger C Tanaka T Morris AP Small K Isaacs A Beekman M Coassin S Lohman K Qi L Kanoni S Pankow JS Uh HW Wu Y Bidulescu A Rasmussen-Torvik LJ Greenwood CM Ladouceur M Grimsby J Manning AK Liu CT Kooner J Mooser VE Vollenweider P Kapur KA Chambers J Wareham NJ Langenberg C Frants R Willems-Vandijk K Oostra BA Willems SM Lamina C Winkler TW Psaty BM Tracy RP Brody J Chen I Viikari J Kähönen M 《PLoS genetics》2012,8(3):e1002607
Circulating levels of adiponectin, a hormone produced predominantly by adipocytes, are highly heritable and are inversely associated with type 2 diabetes mellitus (T2D) and other metabolic traits. We conducted a meta-analysis of genome-wide association studies in 39,883 individuals of European ancestry to identify genes associated with metabolic disease. We identified 8 novel loci associated with adiponectin levels and confirmed 2 previously reported loci (P = 4.5×10−8–1.2×10−43). Using a novel method to combine data across ethnicities (N = 4,232 African Americans, N = 1,776 Asians, and N = 29,347 Europeans), we identified two additional novel loci. Expression analyses of 436 human adipocyte samples revealed that mRNA levels of 18 genes at candidate regions were associated with adiponectin concentrations after accounting for multiple testing (p<3×10−4). We next developed a multi-SNP genotypic risk score to test the association of adiponectin decreasing risk alleles on metabolic traits and diseases using consortia-level meta-analytic data. This risk score was associated with increased risk of T2D (p = 4.3×10−3, n = 22,044), increased triglycerides (p = 2.6×10−14, n = 93,440), increased waist-to-hip ratio (p = 1.8×10−5, n = 77,167), increased glucose two hours post oral glucose tolerance testing (p = 4.4×10−3, n = 15,234), increased fasting insulin (p = 0.015, n = 48,238), but with lower in HDL-cholesterol concentrations (p = 4.5×10−13, n = 96,748) and decreased BMI (p = 1.4×10−4, n = 121,335). These findings identify novel genetic determinants of adiponectin levels, which, taken together, influence risk of T2D and markers of insulin resistance. 相似文献