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971.
Perret M Badiou C Lina G Burbaud S Benito Y Bes M Cottin V Couzon F Juruj C Dauwalder O Goutagny N Diep BA Vandenesch F Henry T 《Cellular microbiology》2012,14(7):1019-1036
Staphylococcus aureus is a major pathogen responsible for both nosocomial and community-acquired infections. Central to its virulence is its ability to secrete haemolysins, pore-forming toxins and cytolytic peptides. The large number of membrane-damaging toxins and peptides produced during S. aureus infections has hindered a precise understanding of their specific roles in diseases. Here, we used comprehensive libraries of recombinant toxins and synthetic cytolytic peptides, of S. aureus mutants and clinical strains to investigate the role of these virulence factors in targeting human macrophages and triggering IL-1β release. We found that the Panton Valentine leukocidin (PVL) is the major trigger of IL-1β release and inflammasome activation in primary human macrophages. The cytolytic peptides, δ-haemolysin and PSMα3; the pore-forming toxins, γ-haemolysin and LukDE; and β-haemolysin synergize with PVL to amplify IL-1β release, indicating that these factors cooperate with PVL to trigger inflammation. PVL(+) S. aureus causes necrotizing pneumonia in children and young adults. The severity of this disease is due to the massive recruitment of neutrophils that cause lung damage. Importantly, we demonstrate that PVL triggers IL-1β release in human alveolar macrophages. Furthermore, IL-1β released by PVL-intoxicated macrophages stimulates the secretion of the neutrophil attracting chemokines, IL-8 and monocyte chemotactic protein-1, by lung epithelial cells. Finally, we show that PVL-induced IL-8/monocyte chemotactic protein-1 release is abolished by the inclusion of IL-1 receptor antagonist (IL-1Ra) in a mixed culture of lung epithelial cells and macrophages. Together, our results identify PVL as the predominant S. aureus secreted factor for triggering inflammasome activation in human macrophages and demonstrate how PVL-intoxicated macrophages orchestrate inflammation in the lung. Finally, our work suggests that anakinra, a synthetic IL-1Ra, may be an effective therapeutic agent to reduce the massive neutrophils infiltration observed during necrotizing pneumonia and decrease the resulting host-mediated lung injury. 相似文献
972.
Faster sequencers, larger datasets, new challenges 总被引:1,自引:0,他引:1
A report on the Advances in Genome Biology and Technology (AGBT) meeting, Marco Island, Florida, USA, 15-18 February 2012. 相似文献
973.
ABSTRACT: BACKGROUND: In food-deceptive orchids of the genera Anacamptis, Neotinea and Orchis floral isolation has been shown to be weak, whereas late-acting reproductive barriers are mostly strong, often restricting hybridization to the F1 generation. Only in a few species hybridization extends beyond the F1 generation, giving rise to hybrid swarms. However, little is known about the abundance of later-generation hybrids and what factors drive their occurrence in hybrid populations. In this study, molecular analyses were combined with detailed morphological measurements in a hybrid population of two closely related Orchis species (Orchis militaris and O. purpurea) to investigate the hypothesis that the abundance of later-generation hybrids is driven by changes in floral characters after hybridization that exert selective pressures that in turn affect hybridization. RESULTS: Both the molecular and morphological data point to extensive genetic and morphological homogenization and asymmetric introgression. Estimating genomic clines from the multi-locus genotype data and testing for deviation from neutrality revealed that 30 out of 113 (27%) AFLP markers significantly deviated from neutral expectations. Plants with large floral displays or plant with flowers that resembled more O. purpurea had higher female fitness than plants with small floral displays or plants with flowers resembling more O. militaris, suggesting that directional selection may have contributed to the observed patterns of introgression. CONCLUSIONS: These results indicate that in closely related orchid species hybridization and gene introgression may be partly driven by selection for floral traits of one of the parental types. However, because some pure individuals were still present in the studied population, the parental species appeared to be sufficiently isolated to survive the challenge of sympatry. 相似文献
974.
B Bed'hom M Vaez JL Coville D Gourichon O Chastel S Follett T Burke F Minvielle 《BMC genomics》2012,13(1):442
ABSTRACT: BACKGROUND: The lavender phenotype in quail is a dilution of both eumelanin and phaeomelanin in feathers that produces a blue-grey colour on a wild-type feather pattern background. It has been previously demonstrated by intergeneric hybridization that the lavender mutation in quail is homologous to the same phenotype in chicken, which is caused by a single base-pair change in exon 1 of MLPH. RESULTS: In this study, we have shown that a mutation of MLPH is also associated with feather colour dilution in quail, but that the mutational event is extremely different. In this species, the lavender phenotype is associated with a non-lethal complex mutation involving three consecutive overlapping chromosomal changes (two inversions and one deletion) that have consequences on the genomic organization of four genes (MLPH and the neighbouring PRLH, RAB17 and LRRFIP1). The deletion of PRLH has no effect on the level of circulating prolactin. Lavender birds have lighter body weight, lower body temperature and increased feed consumption and residual feed intake than wild-type plumage quail, indicating that this complex mutation is affecting the metabolism and the regulation of homeothermy. CONCLUSIONS: An extensive overlapping chromosome rearrangement was associated with a non-pathological Mendelian trait and minor, non deleterious effects in the lavender Japanese quail which is a natural knockout for PRLH. 相似文献
975.
Romolo Caniglia Elena Fabbri Sarah Cubaynes Olivier Gimenez Jean-Dominique Lebreton Ettore Randi 《Conservation Genetics》2012,13(1):53-64
Non-invasive genetic sampling (NGS) is increasingly used to estimate the abundance of rare or elusive species such as the
wolf (Canis lupus), which cannot be directly counted in forested mountain habitats. Wolf individual and familial home ranges are wide, potentially
connected by long-range dispersers, and their populations are intrinsically open. Appropriate demographic estimators are needed,
because the assumptions of homogeneous detection probability and demographic closeness are violated. We compiled the capture–recapture
record of 418 individual wolf genotypes identified from ca. 4,900 non-invasive samples, collected in the northern Italian
Apennines from January 2002 to June 2009. We analysed this dataset using novel capture–recapture multievent models for open
populations that explicitly account for individual detection heterogeneity (IDH). Overall, the detection probability of the
weakly detectable individuals, probably pups, juveniles and migrants (P = 0.08), was ca. six times lower than that of the highly detectable wolves (P = 0.44), probably adults and dominants. The apparent annual survival rate of weakly detectable individuals was lower (Φ = 0.66)
than those of highly detectable wolves (Φ = 0.75). The population mean annual finite rate of increase was λ = 1.05 ± 0.11,
and the mean annual size ranged from N = 117 wolves in 2003 to N = 233 wolves in 2007. This procedure, combining large-scale NGS and multievent IDH demographic models, provides the first
estimates of abundance, multi-annual trend and survival rates for an open large wolf population in the Apennines. These results
contribute to deepen our understanding of wolf population ecology and dynamics, and provide new information to implement sound
long-term conservation plans. 相似文献
976.
977.
978.
Nielen S Vidigal BS Leal-Bertioli SC Ratnaparkhe M Paterson AH Garsmeur O D'Hont A Guimarães PM Bertioli DJ 《Molecular genetics and genomics : MGG》2012,287(1):21-38
Cultivated peanut is an allotetraploid with an AB-genome. In order to learn more of the genomic structure of peanut, we characterized
and studied the evolution of a retrotransposon originally isolated from a resistance gene analog (RGA)-containing bacterial
artificial chromosome (BAC) clone. It is a moderate copy number Ty1-copia retrotransposon from the Bianca lineage and we named it Matita. Fluorescent in situ hybridization (FISH) experiments showed that Matita is mainly located on the distal regions of chromosome arms and is of approximately equal frequency on both A- and B-chromosomes.
Its chromosome-specific hybridization pattern facilitates the identification of individual chromosomes, a useful cytogenetic
tool considering that chromosomes in peanut are mostly metacentric and of similar size. Phylogenetic analysis of Matita elements, molecular dating of transposition events, and an estimation of the evolutionary divergence of the most probable
A- and B-donor species suggest that Matita underwent its last major burst of transposition activity at around the same time of the A- and B-genome divergence about
3.5 million years ago. By probing BAC libraries with overgos probes for Matita, resistance gene analogues, and single- or low-copy genes, it was demonstrated that Matita is not randomly distributed in the genome but exhibits a significant tendency of being more abundant near resistance gene
homologues than near single-copy genes. The described work is a further step towards broadening the knowledge on genomic and
chromosomal structure of peanut and on its evolution. 相似文献
979.
Moussaïd M Guillot EG Moreau M Fehrenbach J Chabiron O Lemercier S Pettré J Appert-Rolland C Degond P Theraulaz G 《PLoS computational biology》2012,8(3):e1002442
In human crowds as well as in many animal societies, local interactions among individuals often give rise to self-organized collective organizations that offer functional benefits to the group. For instance, flows of pedestrians moving in opposite directions spontaneously segregate into lanes of uniform walking directions. This phenomenon is often referred to as a smart collective pattern, as it increases the traffic efficiency with no need of external control. However, the functional benefits of this emergent organization have never been experimentally measured, and the underlying behavioral mechanisms are poorly understood. In this work, we have studied this phenomenon under controlled laboratory conditions. We found that the traffic segregation exhibits structural instabilities characterized by the alternation of organized and disorganized states, where the lifetime of well-organized clusters of pedestrians follow a stretched exponential relaxation process. Further analysis show that the inter-pedestrian variability of comfortable walking speeds is a key variable at the origin of the observed traffic perturbations. We show that the collective benefit of the emerging pattern is maximized when all pedestrians walk at the average speed of the group. In practice, however, local interactions between slow- and fast-walking pedestrians trigger global breakdowns of organization, which reduce the collective and the individual payoff provided by the traffic segregation. This work is a step ahead toward the understanding of traffic self-organization in crowds, which turns out to be modulated by complex behavioral mechanisms that do not always maximize the group's benefits. The quantitative understanding of crowd behaviors opens the way for designing bottom-up management strategies bound to promote the emergence of efficient collective behaviors in crowds. 相似文献
980.
In��s Vigan-Womas Micheline Guillotte Alexandre Juillerat Audrey Hessel Bertrand Raynal Patrick England Jacques H. Cohen Olivier Bertrand Thierry Peyrard Graham A. Bentley Anita Lewit-Bentley Odile Mercereau-Puijalon 《PLoS pathogens》2012,8(7)
The ABO blood group influences susceptibility to severe Plasmodium falciparum malaria. Recent evidence indicates that the protective effect of group O operates by virtue of reduced rosetting of infected red blood cells (iRBCs) with uninfected RBCs. Rosetting is mediated by a subgroup of PfEMP1 adhesins, with RBC binding being assigned to the N-terminal DBL1α1 domain. Here, we identify the ABO blood group as the main receptor for VarO rosetting, with a marked preference for group A over group B, which in turn is preferred to group O RBCs. We show that recombinant NTS-DBL1α1 and NTS-DBL1α1-CIDR1γ reproduce the VarO-iRBC blood group preference and document direct binding to blood group trisaccharides by surface plasmon resonance. More detailed RBC subgroup analysis showed preferred binding to group A1, weaker binding to groups A2 and B, and least binding to groups Ax and O. The 2.8 Å resolution crystal structure of the PfEMP1-VarO Head region, NTS-DBL1α1-CIDR1γ, reveals extensive contacts between the DBL1α1 and CIDR1γ and shows that the NTS-DBL1α1 hinge region is essential for RBC binding. Computer docking of the blood group trisaccharides and subsequent site-directed mutagenesis localized the RBC-binding site to the face opposite to the heparin-binding site of NTS-DBLα1. RBC binding involves residues that are conserved between rosette-forming PfEMP1 adhesins, opening novel opportunities for intervention against severe malaria. By deciphering the structural basis of blood group preferences in rosetting, we provide a link between ABO blood grouppolymorphisms and rosette-forming adhesins, consistent with the selective role of falciparum malaria on human genetic makeup. 相似文献