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991.
Rebecca T. Kimball Edward L. Braun F. Keith Barker Rauri C.K. Bowie Michael J. Braun Jena L. Chojnowski Shannon J. Hackett Kin-Lan Han John Harshman Victoria Heimer-Torres Wallace Holznagel Christopher J. Huddleston Ben D. Marks Kathleen J. Miglia William S. Moore Sushma Reddy Frederick H. Sheldon Jordan V. Smith Christopher C. Witt Tamaki Yuri 《Molecular phylogenetics and evolution》2009,50(3):654-660
992.
A Genome-wide Association Study Identifies Three Loci Associated with Mean Platelet Volume 总被引:2,自引:0,他引:2
Christa Meisinger Holger Prokisch Christian Gieger Nicole Soranzo Divya Mehta Dieter Rosskopf Peter Lichtner Norman Klopp Jonathan Stephens Nicholas A. Watkins Panos Deloukas Andreas Greinacher Wolfgang Koenig Matthias Nauck Christian Rimmbach Henry Vlzke Annette Peters Thomas Illig Willem H. Ouwehand Thomas Meitinger H.-Erich Wichmann Angela Dring 《American journal of human genetics》2009,84(1):66-71
993.
Cordula Zeller Holger Fr?hlich Achim Tresch 《EURASIP Journal on Bioinformatics and Systems Biology》2009,2009(1):195272
Nested effects models (NEMs) are a class of probabilistic models that were designed to reconstruct a hidden signalling structure from a large set of observable effects caused by active interventions into the signalling pathway. We give a more flexible formulation of NEMs in the language of Bayesian networks. Our framework constitutes a natural generalization of the original NEM model, since it explicitly states the assumptions that are tacitly underlying the original version. Our approach gives rise to new learning methods for NEMs, which have been implemented in the /Bioconductor package nem. We validate these methods in a simulation study and apply them to a synthetic lethality dataset in yeast. 相似文献
994.
Dynamics and functional relevance of ammonia-oxidizing archaea in two agricultural soils 总被引:4,自引:0,他引:4
Kristina Schauss reas Focks Sven Leininger Anja Kotzerke Holger Heuer Sören Thiele-Bruhn Shilpi Sharma Berndt-Michael Wilke Michael Matthies Kornelia Smalla Jean Charles Munch Wulf Amelung Martin Kaupenjohann Michael Schloter Christa Schleper 《Environmental microbiology》2009,11(2):446-456
Crucial steps in geochemical cycles are in many cases performed by more than one group of microorganisms, but the significance of this functional redundancy with respect to ecosystem functioning is poorly understood. Ammonia-oxidizing archaea (AOA) and their bacterial counterparts (AOB) are a perfect system to address this question: although performing the same transformation step, they belong to well-separated phylogenetic groups. Using pig manure amended with different concentrations of sulfadiazine (SDZ), an antibiotic that is frequently used in veterinary medicine, it was possible to affect AOB and AOA to different degrees. Addition of manure stimulated growth of AOB in both soils and, interestingly, also growth of AOA was considerably stimulated in one of the soils. The antibiotic treatments decreased the manure effect notably on AOB, whereas AOA were affected to a lower extent. Model calculations concerning the respective proportions of AOA and AOB in ammonia oxidation indicate a substantial contribution of AOA in one of the soils that further increased under the influence of SDZ, hence indicating functional redundancy between AOA and AOB. 相似文献
995.
Carsten Schleh Christian Mühlfeld Karin Pulskamp Andreas Schmiedl Matthias Nassimi Hans D Lauenstein Armin Braun Norbert Krug Veit J Erpenbeck Jens M Hohlfeld 《Respiratory research》2009,10(1):90
Background
Pulmonary surfactant reduces surface tension and is present at the air-liquid interface in the alveoli where inhaled nanoparticles preferentially deposit. We investigated the effect of titanium dioxide (TiO2) nanosized particles (NSP) and microsized particles (MSP) on biophysical surfactant function after direct particle contact and after surface area cycling in vitro. In addition, TiO2 effects on surfactant ultrastructure were visualized.Methods
A natural porcine surfactant preparation was incubated with increasing concentrations (50-500 μg/ml) of TiO2 NSP or MSP, respectively. Biophysical surfactant function was measured in a pulsating bubble surfactometer before and after surface area cycling. Furthermore, surfactant ultrastructure was evaluated with a transmission electron microscope.Results
TiO2 NSP, but not MSP, induced a surfactant dysfunction. For TiO2 NSP, adsorption surface tension (γads) increased in a dose-dependent manner from 28.2 ± 2.3 mN/m to 33.2 ± 2.3 mN/m (p < 0.01), and surface tension at minimum bubble size (γmin) slightly increased from 4.8 ± 0.5 mN/m up to 8.4 ± 1.3 mN/m (p < 0.01) at high TiO2 NSP concentrations. Presence of NSP during surface area cycling caused large and significant increases in both γads (63.6 ± 0.4 mN/m) and γmin (21.1 ± 0.4 mN/m). Interestingly, TiO2 NSP induced aberrations in the surfactant ultrastructure. Lamellar body like structures were deformed and decreased in size. In addition, unilamellar vesicles were formed. Particle aggregates were found between single lamellae.Conclusion
TiO2 nanosized particles can alter the structure and function of pulmonary surfactant. Particle size and surface area respectively play a critical role for the biophysical surfactant response in the lung. 相似文献996.
Sven Hennig Holger M Strauss Katja Vanselow
zkan Yildiz Sabrina Schulze Julia Arens Achim Kramer Eva Wolf 《PLoS biology》2009,7(4)
PERIOD proteins are central components of the Drosophila and mammalian circadian clocks. The crystal structure of a Drosophila PERIOD (dPER) fragment comprising two PER-ARNT-SIM (PAS) domains (PAS-A and PAS-B) and two additional C-terminal α-helices (αE and αF) has revealed a homodimer mediated by intermolecular interactions of PAS-A with tryptophane 482 in PAS-B and helix αF. Here we present the crystal structure of a monomeric PAS domain fragment of dPER lacking the αF helix. Moreover, we have solved the crystal structure of a PAS domain fragment of the mouse PERIOD homologue mPER2. The mPER2 structure shows a different dimer interface than dPER, which is stabilized by interactions of the PAS-B β-sheet surface including tryptophane 419 (equivalent to Trp482dPER). We have validated and quantitatively analysed the homodimer interactions of dPER and mPER2 by site-directed mutagenesis using analytical gel filtration, analytical ultracentrifugation, and co-immunoprecipitation experiments. Furthermore we show, by yeast-two-hybrid experiments, that the PAS-B β-sheet surface of dPER mediates interactions with TIMELESS (dTIM). Our study reveals quantitative and qualitative differences between the homodimeric PAS domain interactions of dPER and its mammalian homologue mPER2. In addition, we identify the PAS-B β-sheet surface as a versatile interaction site mediating mPER2 homodimerization in the mammalian system and dPER-dTIM heterodimer formation in the Drosophila system. 相似文献
997.
Recent publications have described and applied a novel metric that quantifies the
genetic distance of an individual with respect to two population samples, and
have suggested that the metric makes it possible to infer the presence of an
individual of known genotype in a sample for which only the marginal allele
frequencies are known. However, the assumptions, limitations, and utility of
this metric remained incompletely characterized. Here we present empirical tests
of the method using publicly accessible genotypes, as well as analytical
investigations of the method''s strengths and limitations. The results
reveal that the null distribution is sensitive to the underlying assumptions,
making it difficult to accurately calibrate thresholds for classifying an
individual as a member of the population samples. As a result, the
false-positive rates obtained in practice are considerably higher than
previously believed. However, despite the metric''s inadequacies for
identifying the presence of an individual in a sample, our results suggest
potential avenues for future research on tuning this method to problems of
ancestry inference or disease prediction. By revealing both the strengths and
limitations of the proposed method, we hope to elucidate situations in which
this distance metric may be used in an appropriate manner. We also discuss the
implications of our findings in forensics applications and in the protection of
GWAS participant privacy. 相似文献
998.
Understanding foreign speech is difficult, in part because of unusual mappings between sounds and words. It is known that listeners in their native language can use lexical knowledge (about how words ought to sound) to learn how to interpret unusual speech-sounds. We therefore investigated whether subtitles, which provide lexical information, support perceptual learning about foreign speech. Dutch participants, unfamiliar with Scottish and Australian regional accents of English, watched Scottish or Australian English videos with Dutch, English or no subtitles, and then repeated audio fragments of both accents. Repetition of novel fragments was worse after Dutch-subtitle exposure but better after English-subtitle exposure. Native-language subtitles appear to create lexical interference, but foreign-language subtitles assist speech learning by indicating which words (and hence sounds) are being spoken. 相似文献
999.
Antje D. Ebert Mareike Laußmann Sabine Wegehingel Lars Kaderali Holger Erfle Jürgen Reichert Johannes Lechner Hans‐Dietmar Beer Rainer Pepperkok Walter Nickel 《Traffic (Copenhagen, Denmark)》2010,11(6):813-826
Fibroblast growth factor 2 (FGF2) is a potent mitogen that is exported from cells by an endoplasmic reticulum (ER)/Golgi‐independent mechanism. Unconventional secretion of FGF2 occurs by direct translocation across plasma membranes, a process that depends on the phosphoinositide phosphatidylinositol 4,5‐biphosphate (PI(4,5)P2) at the inner leaflet as well as heparan sulfate proteoglycans at the outer leaflet of plasma membranes; however, additional core and regulatory components of the FGF2 export machinery have remained elusive. Here, using a highly effective RNAi screening approach, we discovered Tec kinase as a novel factor involved in unconventional secretion of FGF2. Tec kinase does not affect FGF2 secretion by an indirect mechanism, but rather forms a heterodimeric complex with FGF2 resulting in phosphorylation of FGF2 at tyrosine 82, a post‐translational modification shown to be essential for FGF2 membrane translocation to cell surfaces. Our findings suggest a crucial role for Tec kinase in regulating FGF2 secretion under various physiological conditions and, therefore, provide a new perspective for the development of a novel class of antiangiogenic drugs targeting the formation of the FGF2/Tec complex. 相似文献
1000.
Stalz H Roth U Schleuder D Macht M Haebel S Strupat K Peter-Katalinic J Hanisch FG 《Glycobiology》2006,16(5):402-414
The ancestral galectin from the sponge Geodia cydonium (GCG) is classified on a structural basis to the prototype subfamily, whereas its carbohydrate-binding specificity is related to that of the mammalian chimera-type galectin-3. This dual coordination reveals GCG as a potential precursor of the later evolved galectin subfamilies, which is reflected in the primary structure of the protein. This study provides evidence that GCG is the LECT1 gene product, while neither a previously described LECT2 gene nor a functional LECT2 gene product was found in the specimen under investigation. The electrophoretically separated protein isomers with apparent molecular masses of 13, 15, and 16 kDa correspond to variants of the LECT1 protein-exhibiting peptide sequence polymorphisms that concern critical positions of the carbohydrate recognition domain (13 kDa: Leu51, Asn55, His130, Gly137; 15 kDa: Ser51, Asn55, Asn130, Gly137; 16 kDa: Ser51, Tyr55, Asn130, Glu137). Four residues, highly conserved in the galectin family, are substituted. None of the residues claimed to be involved in interactions with GalNAcalpha1-3 moieties at an extended binding subsite of galectin-3 was identified in the corresponding positions of GCG. Apparently, the substitutions do not confer distinct binding characteristics to the GCG variants as evidenced by binding studies with a recombinantly expressed 15-kDa isoform. The natural isoforms as well as the recombinant 15-kDa isoform oligomerize by the formation of non-covalent heteromeric or homomeric complexes. A phosphorylation of the galectin was confirmed neither by mass spectrometry nor by alkaline phosphatase treatment combined with isoelectric focusing. 相似文献