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41.
Sonya C. Bardswell Friederike Cuello Alexandra J. Rowland Sakthivel Sadayappan Jeffrey Robbins Mathias Gautel Jeffery W. Walker Jonathan C. Kentish Metin Avkiran 《The Journal of biological chemistry》2010,285(8):5674-5682
Protein kinase D (PKD), a serine/threonine kinase with emerging cardiovascular functions, phosphorylates cardiac troponin I (cTnI) at Ser22/Ser23, reduces myofilament Ca2+ sensitivity, and accelerates cross-bridge cycle kinetics. Whether PKD regulates cardiac myofilament function entirely through cTnI phosphorylation at Ser22/Ser23 remains to be established. To determine the role of cTnI phosphorylation at Ser22/Ser23 in PKD-mediated regulation of cardiac myofilament function, we used transgenic mice that express cTnI in which Ser22/Ser23 are substituted by nonphosphorylatable Ala (cTnI-Ala2). In skinned myocardium from wild-type (WT) mice, PKD increased cTnI phosphorylation at Ser22/Ser23 and decreased the Ca2+ sensitivity of force. In contrast, PKD had no effect on the Ca2+ sensitivity of force in myocardium from cTnI-Ala2 mice, in which Ser22/Ser23 were unavailable for phosphorylation. Surprisingly, PKD accelerated cross-bridge cycle kinetics similarly in myocardium from WT and cTnI-Ala2 mice. Because cardiac myosin-binding protein C (cMyBP-C) phosphorylation underlies cAMP-dependent protein kinase (PKA)-mediated acceleration of cross-bridge cycle kinetics, we explored whether PKD phosphorylates cMyBP-C at its PKA sites, using recombinant C1C2 fragments with or without site-specific Ser/Ala substitutions. Kinase assays confirmed that PKA phosphorylates Ser273, Ser282, and Ser302, and revealed that PKD phosphorylates only Ser302. Furthermore, PKD phosphorylated Ser302 selectively and to a similar extent in native cMyBP-C of skinned myocardium from WT and cTnI-Ala2 mice, and this phosphorylation occurred throughout the C-zones of sarcomeric A-bands. In conclusion, PKD reduces myofilament Ca2+ sensitivity through cTnI phosphorylation at Ser22/Ser23 but accelerates cross-bridge cycle kinetics by a distinct mechanism. PKD phosphorylates cMyBP-C at Ser302, which may mediate the latter effect. 相似文献
42.
Alexandra S. Solovyova Jonathan A. Pointon Paul R. Race Wendy D. Smith Michael A. Kehoe Mark J. Banfield 《European biophysics journal : EBJ》2010,39(3):469-480
Adhesion of the serotype M1 Streptococcus pyogenes strain SF370 to human tonsil explants and cultured keratinocytes requires extended polymeric surface structures called pili.
In this important human pathogen, pili are assembled from three protein subunits: Spy0125, Spy0128 and Spy0130 through the
action of sortase enzymes. For this study, the structural properties of these pili proteins have been investigated in solution.
Spy0125 and Spy0128 display characteristics of globular, folded proteins. Circular dichroism suggests a largely β-sheet composition
for Spy0128 and Spy0125; Spy0130 appears to contain little secondary structure. Each of the proteins adopts a monodisperse,
monomeric state in solution as assessed by analytical ultracentrifugation. Further, small-angle X-ray scattering curves for
Spy0125, Spy0128 and Spy0130 suggest each protein adopts an elongated shape, likely comprised of two domains, with similar
maximal dimensions. Based on the scattering data, dummy atom models of each of the pili subunits have been reconstructed ab
initio. This study provides the first insights into the structure of Streptococcus pyogenes minor pili subunits, and possible implications for protein function are discussed. 相似文献
43.
Nikolay?V.?MaximovichEmail author Alexandra?V.?Guerassimova 《Helgoland Marine Research》2003,57(2):91-99
Dynamics of Mya arenaria beds in two bights of the Chupa Inlet (Kandalaksha Bay, White Sea) were studied on a long-term basis. Observations were carried
out at 1– to 3-year intervals from 1979 up to 1999. The studied soft-shell clam beds were characterised by a substantial instability
of age structure. Since 1988, only one year-class has dominated in the beds while other generations have been scarce and recruitment
was not observed. This pattern of Mya bed dynamics was related neither to interannual environmental changes nor to differential reproduction success or predation
effects in the benthic assemblages. Favourable conditions for spat formation in 1988 (low abundance of other M. arenaria generations), as well as for juvenile survival during the following winter, resulted in high abundance of juveniles in both
investigated locations in 1989. The mortality rate (μ) in this 1988 generation varied throughout the period of investigation and was related to age. The mortality level decreased
for the first 2–4 years of the life cycle, then stabilised for the next 3–4 years, and eventually increased in subsequent
years. Overall μ values ranged from 0 to 1.68 year–1. The oldest specimens observed were 17 years old and had a maximum shell length of 79 mm. Significant differences in average
growth rates were observed between molluscs of different locations.
Communicated by H.-D. Franke 相似文献
44.
Chartier-Harlin MC Dachsel JC Vilariño-Güell C Lincoln SJ Leprêtre F Hulihan MM Kachergus J Milnerwood AJ Tapia L Song MS Le Rhun E Mutez E Larvor L Duflot A Vanbesien-Mailliot C Kreisler A Ross OA Nishioka K Soto-Ortolaza AI Cobb SA Melrose HL Behrouz B Keeling BH Bacon JA Hentati E Williams L Yanagiya A Sonenberg N Lockhart PJ Zubair AC Uitti RJ Aasly JO Krygowska-Wajs A Opala G Wszolek ZK Frigerio R Maraganore DM Gosal D Lynch T Hutchinson M Bentivoglio AR Valente EM Nichols WC Pankratz N 《American journal of human genetics》2011,(3):140-406
Genome-wide analysis of a multi-incident family with autosomal-dominant parkinsonism has implicated a locus on chromosomal region 3q26-q28. Linkage and disease segregation is explained by a missense mutation c.3614G>A (p.Arg1205His) in eukaryotic translation initiation factor 4-gamma (EIF4G1). Subsequent sequence and genotype analysis identified EIF4G1 c.1505C>T (p.Ala502Val), c.2056G>T (p.Gly686Cys), c.3490A>C (p.Ser1164Arg), c.3589C>T (p.Arg1197Trp) and c.3614G>A (p.Arg1205His) substitutions in affected subjects with familial parkinsonism and idiopathic Lewy body disease but not in control subjects. Despite different countries of origin, persons with EIF4G1 c.1505C>T (p.Ala502Val) or c.3614G>A (p.Arg1205His) mutations appear to share haplotypes consistent with ancestral founders. eIF4G1 p.Ala502Val and p.Arg1205His disrupt eIF4E or eIF3e binding, although the wild-type protein does not, and render mutant cells more vulnerable to reactive oxidative species. EIF4G1 mutations implicate mRNA translation initiation in familial parkinsonism and highlight a convergent pathway for monogenic, toxin and perhaps virally-induced Parkinson disease. 相似文献
45.
Devedjiev Y Surendranath Y Derewenda U Gabrys A Cooper DR Zhang RG Lezondra L Joachimiak A Derewenda ZS 《Journal of molecular biology》2004,343(2):395-406
The crystal structure of the Bacillus subtilis YkoF gene product, a protein involved in the hydroxymethyl pyrimidine (HMP) salvage pathway, was solved by the multiwavelength anomalous dispersion (MAD) method and refined with data extending to 1.65 A resolution. The atomic model of the protein shows a homodimeric association of two polypeptide chains, each containing an internal repeat of a ferredoxin-like betaalphabetabetaalphabeta fold, as seen in the ACT and RAM-domains. Each repeat shows a remarkable similarity to two members of the COG0011 domain family, the MTH1187 and YBL001c proteins, the crystal structures of which were recently solved by the Northeast Structural Genomics Consortium. Two YkoF monomers form a tightly associated dimer, in which the amino acid residues forming the interface are conserved among family members. A putative small-ligand binding site was located within each repeat in a position analogous to the serine-binding site of the ACT-domain of the Escherichia coli phosphoglycerate dehydrogenase. Genetic data suggested that this could be a thiamin or HMP-binding site. Calorimetric data confirmed that YkoF binds two thiamin molecules with varying affinities and a thiamine-YkoF complex was obtained by co-crystallization. The atomic model of the complex was refined using data to 2.3 A resolution and revealed a unique H-bonding pattern that constitutes the molecular basis of specificity for the HMP moiety of thiamin. 相似文献
46.
Artoni RF Vicari MR Endler AL Cavallaro ZI de Jesus CM de Almeida MC Moreira-Filho O Bertollo LA 《Genetica》2006,127(1-3):277-284
B chromosomes in Prochilodus lineatus, a migratory neotropical fish, were analyzed in a comparative study among populations from the Dourada lagoon (State of Paraná, Brazil) and from Mogi-Guaçu river (State of São Paulo, Brazil). The data on C-banding and fluorescent in situ hybridization with a satellite DNA probe (SATH1), indicate that the small metacentric B chromosome might correspond to an isochromosome. On the other hand, both populations presented a distinct set of B chromosomes, differentiated either by their number and by the presence of variant B types in the population from Mogi-Guaçu river. The present results indicate that the B chromosomes of P. lineatus should have an ancient origin, and have undergone a differential evolutionary pathway among distinct populations. 相似文献
47.
48.
49.
Ahlqvist KJ Hämäläinen RH Yatsuga S Uutela M Terzioglu M Götz A Forsström S Salven P Angers-Loustau A Kopra OH Tyynismaa H Larsson NG Wartiovaara K Prolla T Trifunovic A Suomalainen A 《Cell metabolism》2012,15(1):100-109
Somatic stem cell (SSC) dysfunction is typical for different progeroid phenotypes in mice with genomic DNA repair defects. MtDNA mutagenesis in mice with defective Polg exonuclease activity also leads to progeroid symptoms, by an unknown mechanism. We found that Polg-Mutator mice had neural (NSC) and hematopoietic progenitor (HPC) dysfunction already from embryogenesis. NSC self-renewal was decreased in vitro, and quiescent NSC amounts were reduced in vivo. HPCs showed abnormal lineage differentiation leading to anemia and lymphopenia. N-acetyl-L-cysteine treatment rescued both NSC and HPC abnormalities, suggesting that subtle ROS/redox changes, induced by mtDNA mutagenesis, modulate SSC function. Our results show that mtDNA mutagenesis affected SSC function early but manifested as respiratory chain deficiency in nondividing tissues in old age. Deletor mice, having mtDNA deletions in postmitotic cells and no progeria, had normal SSCs. We propose that SSC compartment is sensitive to mtDNA mutagenesis, and that mitochondrial dysfunction in SSCs can underlie progeroid manifestations. 相似文献
50.