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991.
Bollinger T Leutz A Leliavski A Skrum L Kovac J Bonacina L Benedict C Lange T Westermann J Oster H Solbach W 《PloS one》2011,6(12):e29801
Though it has been shown that immunological functions of CD4+ T cells are time of day-dependent, the underlying molecular mechanisms remain largely obscure. To address the question whether T cells themselves harbor a functional clock driving circadian rhythms of immune function, we analyzed clock gene expression by qPCR in unstimulated CD4+ T cells and immune responses of PMA/ionomycin stimulated CD4+ T cells by FACS analysis purified from blood of healthy subjects at different time points throughout the day. Molecular clock as well as immune function was further analyzed in unstimulated T cells which were cultured in serum-free medium with circadian clock reporter systems. We found robust rhythms of clock gene expression as well as, after stimulation, IL-2, IL-4, IFN-γ production and CD40L expression in freshly isolated CD4+ T cells. Further analysis of IFN-γ and CD40L in cultivated T cells revealed that these parameters remain rhythmic in vitro. Moreover, circadian luciferase reporter activity in CD4+ T cells and in thymic sections from PER2::LUCIFERASE reporter mice suggest that endogenous T cell clock rhythms are self-sustained under constant culture conditions. Microarray analysis of stimulated CD4+ T cell cultures revealed regulation of the NF-κB pathway as a candidate mechanism mediating circadian immune responses. Collectively, these data demonstrate for the first time that CD4+ T cell responses are regulated by an intrinsic cellular circadian oscillator capable of driving rhythmic CD4+ T cell immune responses. 相似文献
992.
White S Ohnesorg T Notini A Roeszler K Hewitt J Daggag H Smith C Turbitt E Gustin S van den Bergen J Miles D Western P Arboleda V Schumacher V Gordon L Bell K Bengtsson H Speed T Hutson J Warne G Harley V Koopman P Vilain E Sinclair A 《PloS one》2011,6(3):e17793
Disorders of sex development (DSD), ranging in severity from mild genital abnormalities to complete sex reversal, represent a major concern for patients and their families. DSD are often due to disruption of the genetic programs that regulate gonad development. Although some genes have been identified in these developmental pathways, the causative mutations have not been identified in more than 50% 46,XY DSD cases. We used the Affymetrix Genome-Wide Human SNP Array 6.0 to analyse copy number variation in 23 individuals with unexplained 46,XY DSD due to gonadal dysgenesis (GD). Here we describe three discrete changes in copy number that are the likely cause of the GD. Firstly, we identified a large duplication on the X chromosome that included DAX1 (NR0B1). Secondly, we identified a rearrangement that appears to affect a novel gonad-specific regulatory region in a known testis gene, SOX9. Surprisingly this patient lacked any signs of campomelic dysplasia, suggesting that the deletion affected expression of SOX9 only in the gonad. Functional analysis of potential SRY binding sites within this deleted region identified five putative enhancers, suggesting that sequences additional to the known SRY-binding TES enhancer influence human testis-specific SOX9 expression. Thirdly, we identified a small deletion immediately downstream of GATA4, supporting a role for GATA4 in gonad development in humans. These CNV analyses give new insights into the pathways involved in human gonad development and dysfunction, and suggest that rearrangements of non-coding sequences disturbing gene regulation may account for significant proportion of DSD cases. 相似文献
993.
994.
Wang Z Nilsson RH Lopez-Giraldez F Zhuang WY Dai YC Johnston PR Townsend JP 《PloS one》2011,6(4):e19039
An abundance of novel fungal lineages have been indicated by DNA sequencing of the nuclear ribosomal ITS region from environmental samples such as soil and wood. Although phylogenetic analysis of these novel lineages is a key component of unveiling the structure and diversity of complex communities, such analyses are rare for environmental ITS data due to the difficulties of aligning this locus across significantly divergent taxa. One potential approach to this issue is simultaneous alignment and tree estimation. We targeted divergent ITS sequences of the earth tongue fungi (Geoglossomycetes), a basal class in the Ascomycota, to assess the performance of SATé, recent software that combines progressive alignment and tree building. We found that SATé performed well in generating high-quality alignments and in accurately estimating the phylogeny of earth tongue fungi. Drawing from a data set of 300 sequences of earth tongues and progressively more distant fungal lineages, 30 insufficiently identified ITS sequences from the public sequence databases were assigned to the Geoglossomycetes. The association between earth tongues and plants has been hypothesized for a long time, but hard evidence is yet to be collected. The ITS phylogeny showed that four ectomycorrhizal isolates shared a clade with Geoglossum but not with Trichoglossum earth tongues, pointing to the significant potential inherent to ecological data mining of environmental samples. Environmental sampling holds the key to many focal questions in mycology, and simultaneous alignment and tree estimation, as performed by SATé, can be a highly efficient companion in that pursuit. 相似文献
995.
Jannes Muenchow Achim Bräuning Eric Frank Rodríguez Henrik von Wehrden 《Biotropica》2013,45(5):557-566
Tropical arid to semi‐arid ecosystems are nearly as diverse as more humid forests and occupy large parts of the tropics. In comparison, however, they are vastly understudied. For instance, fog precipitation alone supports a unique vegetation formation, locally termed lomas, on coastal mountains in the Peruvian desert. To effectively protect these highly endemic and threatened ecosystems, we must increase our understanding of their diversity patterns in relation to environmental factors. Consequently, we recorded all vascular species from 100 random 4 × 4 m plots on the fog‐exposed southern slope of the mountain Mongón. We used topographic and remotely sensed covariates in statistical models to generate spatial predictions of alpha diversity and plant species' distribution probabilities. Altitude was the most important predictor in all models and may represent fog moisture levels. Other significant covariates in the models most likely refer also to water availability but on a finer spatial scale. Additionally, model‐based clustering revealed five altitudinal vegetation zones. This study contributes to a better spatial understanding of the biodiversity and spatial arrangement of vegetation belts of the largely unknown but highly unique lomas formations. Furthermore, mapping species richness and plant species' distributions could support a long‐needed lomas strategic conservation scheme. 相似文献
996.
Capsule Nest survival rates could not be explained by distance to habitat edges or other features used by predators. Aims To investigate if predation on Redshank nests was affected by habitat characteristics at a local scale. Methods We examined survival rates of Redshank nests on coastal meadows on the Baltic island of Gotland, Sweden, over two breeding seasons. We analysed nest survival rates in relation to several habitat characteristics that may benefit predators searching for nests. We examined existing studies concerning predation rates on wader nests in relation to edges and habitat features potentially used by avian predators. Results We found no significant effects of distance to habitat edge or to nearest potential lookout for avian predators or to shoreline. Abundance of Lapwings Vanellus vanellus, an aggressive species with active nest-defence, did not have any significant effect on nest survival rate, nor did vegetation concealment of nests. Nest survival rates were significantly different between years and lower later in the season. Conclusions There is only weak support for general effects on wader nest predation rates of proximity to edges and features used by avian predators. Simple mechanical management actions such as removal of trees and bushes on coastal meadows may not directly, and by itself, result in higher reproductive success of waders. Further understanding is needed of the behaviour of predators and the composition of the predator community in different landscapes in order to increase the efficiency of management actions to remove threats to vulnerable species on coastal meadows. 相似文献
997.
Thomas A. Gerken Leslie Revoredo Joseph J. C. Thome Lawrence A. Tabak Malene Bech Vester-Christensen Henrik Clausen Gagandeep K. Gahlay Donald L. Jarvis Roy W. Johnson Heather A. Moniz Kelley Moremen 《The Journal of biological chemistry》2013,288(27):19900-19914
Mucin type O-glycosylation is initiated by a large family of polypeptide GalNAc transferases (ppGalNAc Ts) that add α-GalNAc to the Ser and Thr residues of peptides. Of the 20 human isoforms, all but one are composed of two globular domains linked by a short flexible linker: a catalytic domain and a ricin-like lectin carbohydrate binding domain. Presently, the roles of the catalytic and lectin domains in peptide and glycopeptide recognition and specificity remain unclear. To systematically study the role of the lectin domain in ppGalNAc T glycopeptide substrate utilization, we have developed a series of novel random glycopeptide substrates containing a single GalNAc-O-Thr residue placed near either the N or C terminus of the glycopeptide substrate. Our results reveal that the presence and N- or C-terminal placement of the GalNAc-O-Thr can be important determinants of overall catalytic activity and specificity that differ between transferase isoforms. For example, ppGalNAc T1, T2, and T14 prefer C-terminally placed GalNAc-O-Thr, whereas ppGalNAc T3 and T6 prefer N-terminally placed GalNAc-O-Thr. Several transferase isoforms, ppGalNAc T5, T13, and T16, display equally enhanced N- or C-terminal activities relative to the nonglycosylated control peptides. This N- and/or C-terminal selectivity is presumably due to weak glycopeptide binding to the lectin domain, whose orientation relative to the catalytic domain is dynamic and isoform-dependent. Such N- or C-terminal glycopeptide selectivity provides an additional level of control or fidelity for the O-glycosylation of biologically significant sites and suggests that O-glycosylation may in some instances be exquisitely controlled. 相似文献
998.
Rachael Baker Emily M. Wilkerson Kazutaka Sumita Daniel G. Isom Atsuo T. Sasaki Henrik G. Dohlman Sharon L. Campbell 《The Journal of biological chemistry》2013,288(52):36856-36862
Ras GTPases are signaling switches that control critical cellular processes including gene expression, differentiation, and apoptosis. The major Ras isoforms (K, H, and N) contain a conserved core GTPase domain, but have distinct biological functions. Among the three Ras isoforms there are clear differences in post-translational regulation, which contribute to differences in localization and signaling output. Modification by ubiquitination was recently reported to activate Ras signaling in cells, but the mechanisms of activation are not well understood. Here, we show that H-Ras is activated by monoubiquitination and that ubiquitination at Lys-117 accelerates intrinsic nucleotide exchange, thereby promoting GTP loading. This mechanism of Ras activation is distinct from K-Ras monoubiquitination at Lys-147, which leads to impaired regulator-mediated GTP hydrolysis. These findings reveal that different Ras isoforms are monoubiquitinated at distinct sites, with distinct mechanisms of action, but with a common ability to chronically activate the protein in the absence of a receptor signal or oncogenic mutation. 相似文献
999.
Daniel H. Madsen Daniel Leonard Andrius Masedunskas Amanda Moyer Henrik Jessen Jürgensen Diane E. Peters Panomwat Amornphimoltham Arul Selvaraj Susan S. Yamada David A. Brenner Sven Burgdorf Lars H. Engelholm Niels Behrendt Kenn Holmbeck Roberto Weigert Thomas H. Bugge 《The Journal of cell biology》2013,202(6):951-966
Tissue remodeling processes critically depend on the timely removal and remodeling of preexisting collagen scaffolds. Nevertheless, many aspects related to the turnover of this abundant extracellular matrix component in vivo are still incompletely understood. We therefore took advantage of recent advances in optical imaging to develop an assay to visualize collagen turnover in situ and identify cell types and molecules involved in this process. Collagen introduced into the dermis of mice underwent cellular endocytosis in a partially matrix metalloproteinase–dependent manner and was subsequently routed to lysosomes for complete degradation. Collagen uptake was predominantly executed by a quantitatively minor population of M2-like macrophages, whereas more abundant Col1a1-expressing fibroblasts and Cx3cr1-expressing macrophages internalized collagen at lower levels. Genetic ablation of the collagen receptors mannose receptor (Mrc1) and urokinase plasminogen activator receptor–associated protein (Endo180 and Mrc2) impaired this intracellular collagen degradation pathway. This study demonstrates the importance of receptor-mediated cellular uptake to collagen turnover in vivo and identifies a key role of M2-like macrophages in this process. 相似文献
1000.
Henrik G?rdsvoll Mette C. Kriegbaum Emil P. Hertz Warner Alpízar-Alpízar Michael Ploug 《The journal of histochemistry and cytochemistry》2013,61(11):802-813
Several members of the Ly-6/uPAR (LU)-protein domain family are differentially expressed in human squamous epithelia. In some cases, they even play important roles in maintaining skin homeostasis, as exemplified by the secreted single domain member, SLURP-1, the deficiency of which is associated with the development of palmoplantar hyperkeratosis in the congenital skin disorder Mal de Meleda. In the present study, we have characterized a new member of the LU-protein domain family, which we find to be predominantly expressed in the stratum granulosum of human skin, thus resembling the expression of SLURP-1. In accordance with its expression pattern, we denote this protein product, which is encoded by the LYPD5 gene, as Haldisin (human antigen with LU-domains expressed in skin). Two of the five human glycolipid-anchored membrane proteins with multiple LU-domains characterized so far are predominantly confined to squamous epithelia (i.e., C4.4A), to stratum spinosum, and Haldisin to stratum granulosum under normal homeostatic conditions. Whether Haldisin is a prognostic biomarker for certain epithelial malignancies, like C4.4A and SLURP-1, remains to be explored. 相似文献