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M. Alings M. D. Smit M. L. Moes H. J. G. M. Crijns J. G. P. Tijssen J. Brügemann H. L. Hillege D. A. Lane G. Y. H. Lip J. R. L. M. Smeets R. G. Tieleman R. Tukkie F. F. Willems R. A. Vermond D. J. Van Veldhuisen I. C. Van Gelder 《Netherlands heart journal》2013,21(7-8):354-363
Background
Rhythm control for atrial fibrillation (AF) is cumbersome because of its progressive nature caused by structural remodelling. Upstream therapy refers to therapeutic interventions aiming to modify the atrial substrate, leading to prevention of AF.Objective
The Routine versus Aggressive upstream rhythm Control for prevention of Early AF in heart failure (RACE 3) study hypothesises that aggressive upstream rhythm control increases persistence of sinus rhythm compared with conventional rhythm control in patients with early AF and mild-to-moderate early systolic or diastolic heart failure undergoing electrical cardioversion.Design
RACE 3 is a prospective, randomised, open, multinational, multicenter trial. Upstream rhythm control consists of angiotensin converting enzyme inhibitors and/or angiotensin receptor blockers, mineralocorticoid receptor antagonists, statins, cardiac rehabilitation therapy, and intensive counselling on dietary restrictions, exercise maintenance, and drug adherence. Conventional rhythm control consists of routine rhythm control therapy without cardiac rehabilitation therapy and intensive counselling. In both arms, every effort is made to keep patients in the rhythm control strategy, and ion channel antiarrhythmic drugs or pulmonary vein ablation may be instituted if AF relapses. Total inclusion will be 250 patients. If upstream therapy proves to be effective in improving maintenance of sinus rhythm, it could become a new approach to rhythm control supporting conventional pharmacological and non-pharmacological rhythm control. 相似文献34.
Niels Van Steenkiste Bart Tessens Wim Willems Thierry Backeljau Ulf Jondelius Tom Artois 《PloS one》2013,8(3)
In this study we elaborate the phylogeny of Dalytyphloplanida based on complete 18S rDNA (156 sequences) and partial 28S rDNA (125 sequences), using a Maximum Likelihood and a Bayesian Inference approach, in order to investigate the origin of a limnic or limnoterrestrial and of a symbiotic lifestyle in this large group of rhabditophoran flatworms. The results of our phylogenetic analyses and ancestral state reconstructions indicate that dalytyphloplanids have their origin in the marine environment and that there was one highly successful invasion of the freshwater environment, leading to a large radiation of limnic and limnoterrestrial dalytyphloplanids. This monophyletic freshwater clade, Limnotyphloplanida, comprises the taxa Dalyelliidae, Temnocephalida, and most Typhloplanidae. Temnocephalida can be considered ectosymbiotic Dalyelliidae as they are embedded within this group. Secondary returns to brackish water and marine environments occurred relatively frequently in several dalyeliid and typhloplanid taxa. Our phylogenies also show that, apart from the Limnotyphloplanida, there have been only few independent invasions of the limnic environment, and apparently these were not followed by spectacular speciation events. The distinct phylogenetic positions of the symbiotic taxa also suggest multiple origins of commensal and parasitic life strategies within Dalytyphloplanida. The previously established higher-level dalytyphloplanid clades are confirmed in our topologies, but many of the traditional families are not monophyletic. Alternative hypothesis testing constraining the monophyly of these families in the topologies and using the approximately unbiased test, also statistically rejects their monophyly. 相似文献
35.
Sunita S. Balla-Jhagjhoorsingh Davide Corti Leo Heyndrickx Elisabeth Willems Katleen Vereecken David Davis Guido Vanham 《PloS one》2013,8(7)
Immunogen design for HIV-1 vaccines could be based on epitope identification of naturally occurring neutralizing antibodies in infected patients. A tier 2 neutralizing monoclonal antibody (mAb), HJ16 recognizes a new epitope in the CD4 binding site (CD4bs) region that only partially overlaps with the b12 epitope. We aimed to identify the critical binding site by resistance induction in a sensitive primary CRF02_AG strain. In four independent dose-escalation studies, the N276D mutation was consistently the only alteration found and it was confirmed to be responsible for resistance to HJ16 by site-directed mutagenesis in envelopes (envs) of the homologous CRF02_AG, as well as of a subtype A and a subtype C primary isolate. This mutation removes an N-linked glycosylation site. The effect of N276D was very selective, as it failed to confer resistance to a range of other entry inhibitors. Remarkably, sensitivity to the CD4bs VRC01 and VRC03 mAbs was increased in the N276D mutated viruses. These data indicate that binding of the CD4bs specific HJ16 mAb critically depends on the interaction with the N276-glycan, thus indicating that HJ16 is the first glycan dependent CD4bs-specific mAb. 相似文献
36.
Janna A. van Diepen Rinke Stienstra Irene O. C. M. Vroegrijk Sjoerd A. A. van den Berg Daniela Salvatori Guido J. Hooiveld Sander Kersten Cees J. Tack Mihai G. Netea Johannes W.A. Smit Leo A. B. Joosten Louis M. Havekes Ko Willems van Dijk Patrick C. N. Rensen 《Journal of lipid research》2013,54(2):448-456
Caspase-1 is known to activate the proinflammatory cytokines IL-1β and IL-18. Additionally, it can cleave other substrates, including proteins involved in metabolism. Recently, we showed that caspase-1 deficiency in mice strongly reduces high-fat diet-induced weight gain, at least partly caused by an increased energy production. Increased feces secretion by caspase-1-deficient mice suggests that lipid malabsorption possibly further reduces adipose tissue mass. In this study we investigated whether caspase-1 plays a role in triglyceride-(TG)-rich lipoprotein metabolism using caspase-1-deficient and wild-type mice. Caspase-1 deficiency reduced the postprandial TG response to an oral lipid load, whereas TG-derived fatty acid (FA) uptake by peripheral tissues was not affected, demonstrated by unaltered kinetics of [3H]TG-labeled very low-density lipoprotein (VLDL)-like emulsion particles. An oral gavage of [3H]TG-containing olive oil revealed that caspase-1 deficiency reduced TG absorption and subsequent uptake of TG-derived FA in liver, muscle, and adipose tissue. Similarly, despite an elevated hepatic TG content, caspase-1 deficiency reduced hepatic VLDL-TG production. Intestinal and hepatic gene expression analysis revealed that caspase-1 deficiency did not affect FA oxidation or FA uptake but rather reduced intracellular FA transport, thereby limiting lipid availability for the assembly and secretion of TG-rich lipoproteins. The current study reveals a novel function for caspase-1, or caspase-1-cleaved substrates, in controlling intestinal TG absorption and hepatic TG secretion. 相似文献
37.
Background
When two targets are presented in close temporal succession, the majority of people frequently fail to report the second target. This phenomenon, known as the ‘attentional blink’ (AB), has been a major topic in attention research for the past twenty years because it is informative about the rate at which stimuli can be encoded into consciously accessible representations. An aspect of the AB that has long been ignored, however, is individual differences.Methodology/Principal Findings
Here we compare a group of blinkers (who show an AB) and non-blinkers (who show little or no AB), and investigate the boundary conditions of the non-blinkers'' remarkable ability. Second, we directly test the properties of temporal selection by analysing response errors, allowing us to uncover individual differences in suppression, delay, and diffusion of selective attention across time. Thirdly, we test the hypothesis that information concerning temporal order is compromised when an AB is somehow avoided. Surprisingly, compared to earlier studies, only a modest amount of suppression was found for blinkers. Non-blinkers showed no suppression, were more precise in selecting the second target, and made less order reversals than blinkers did. In contrast, non-blinkers made relatively more intrusions and showed a selection delay when the second target immediately followed the first target (at lag 1).Conclusion/Significance
The findings shed new light on the mechanisms that may underlie individual differences in selective attention. The notable ability of non-blinkers to accurately perceive targets presented in close temporal succession might be due to a relatively faster and more precise target selection process compared to large blinkers. 相似文献38.
Wendy W. J. de Leng Christa G. Gadellaa-van Hooijdonk Fran?oise A. S. Barendregt-Smouter Marco J. Koudijs Ies Nijman John W. J. Hinrichs Edwin Cuppen Stef van Lieshout Robert D. Loberg Maja de Jonge Emile E. Voest Roel A. de Weger Neeltje Steeghs Marlies H. G. Langenberg Stefan Sleijfer Stefan M. Willems Martijn P. Lolkema 《PloS one》2016,11(2)
Background
Targeted Next Generation Sequencing (NGS) offers a way to implement testing of multiple genetic aberrations in diagnostic pathology practice, which is necessary for personalized cancer treatment. However, no standards regarding input material have been defined. This study therefore aimed to determine the effect of the type of input material (e.g. formalin fixed paraffin embedded (FFPE) versus fresh frozen (FF) tissue) on NGS derived results. Moreover, this study aimed to explore a standardized analysis pipeline to support consistent clinical decision-making.Method
We used the Ion Torrent PGM sequencing platform in combination with the Ion AmpliSeq Cancer Hotspot Panel v2 to sequence frequently mutated regions in 50 cancer related genes, and validated the NGS detected variants in 250 FFPE samples using standard diagnostic assays. Next, 386 tumour samples were sequenced to explore the effect of input material on variant detection variables. For variant calling, Ion Torrent analysis software was supplemented with additional variant annotation and filtering.Results
Both FFPE and FF tissue could be sequenced reliably with a sensitivity of 99.1%. Validation showed a 98.5% concordance between NGS and conventional sequencing techniques, where NGS provided both the advantage of low input DNA concentration and the detection of low-frequency variants. The reliability of mutation analysis could be further improved with manual inspection of sequence data.Conclusion
Targeted NGS can be reliably implemented in cancer diagnostics using both FFPE and FF tissue when using appropriate analysis settings, even with low input DNA. 相似文献39.
40.
Mechanisms of leukemogenesis induced by bovine leukemia virus: prospects for novel anti-retroviral therapies in human 总被引:1,自引:0,他引:1
Nicolas Gillet Arnaud Florins Mathieu Boxus Catherine Burteau Annamaria Nigro Fabian Vandermeers Hervé Balon Amel-Baya Bouzar Julien Defoiche Arsène Burny Michal Reichert Richard Kettmann Luc Willems 《Retrovirology》2007,4(1):1-32
In 1871, the observation of yellowish nodules in the enlarged spleen of a cow was considered to be the first reported case of bovine leukemia. The etiological agent of this lymphoproliferative disease, bovine leukemia virus (BLV), belongs to the deltaretrovirus genus which also includes the related human T-lymphotropic virus type 1 (HTLV-1). This review summarizes current knowledge of this viral system, which is important as a model for leukemogenesis. Recently, the BLV model has also cast light onto novel prospects for therapies of HTLV induced diseases, for which no satisfactory treatment exists so far. 相似文献