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61.
Steven Wainwright Clare Williams Mike Michael Bobbie Farsides Alan Cribb 《New genetics and society》2013,32(3):251-254
Abstrat In this paper we discuss genetic discourses and practices in stem cell science. We report on how biomedical scientists, in both the UK and the USA, view the scientific literature and their own experimental research in the emerging field of human embryonic stem (hES) cells. We focus on the genetic manipulation of stem cells to make specialized (beta) cells as a potential cure for diabetes. We draw on Gieryn's notion of boundary work as an analytical motif, and suggest this is a productive way to theorize boundary crossings in the shifting landscapes of expectations in the field of new medical technologies. We argue that initial expectations of a revolution in regenerative medicine have been damped down by the difficulties of making insulin producing pancreatic beta cells from stem cells. We contend the consequent shifts in expectations have led to the emergence of other more radical experimental strategies (such as using oncogenes) in the search for potential cures for Type 1 diabetes. In conclusion, we argue that regenerative medicine is a fruitful example of the shaping of contested biomedical landscapes and we contend that embryonic stem cells are a productive case study of the interactions between genetics, science and society. 相似文献
62.
Sara Borin Francesca Mapelli Eleonora Rolli Bongkeun Song Craig Tobias Markus C. Schmid Gert J. De Lange Gert J. Reichart Stefan Schouten Mike Jetten Daniele Daffonchio 《Extremophiles : life under extreme conditions》2013,17(2):289-299
To extend the knowledge of anaerobic ammonium oxidation (anammox) habitats, bacterial communities were examined in two hypersaline sulphidic basins in Eastern Mediterranean Sea. The 2 m thick seawater–brine haloclines of the deep anoxic hypersaline basins Bannock and L’Atalante were sampled in intervals of 10 cm with increasing salinity. 15N isotope pairing incubation experiments showed the production of 29N2 and 30N2 gases in the chemoclines, ranging from 6.0 to 9.2 % salinity of the L’Atalante basin. Potential anammox rates ranged from 2.52 to 49.65 nmol N2 L?1 day?1 while denitrification was a major N2 production pathway, accounting for more than 85.5 % of total N2 production. Anammox-related 16S rRNA genes were detected along the L’Atalante and Bannock haloclines up to 24 % salinity, and the amplification of the hydrazine synthase genes (hzsA) further confirmed the presence of anammox bacteria in Bannock. Fluorescence in situ hybridisation and sequence analysis of 16S rRNA genes identified representatives of the marine anammox genus ‘Candidatus Scalindua’ and putatively new operational taxonomic units closely affiliated to sequences retrieved in marine environments that have documented anammox activity. ‘Scalindua brodae’ like sequences constituted up to 84.4 % of the sequences retrieved from Bannock. The anammox community in L’Atalante was different than in Bannock and was stratified according to salinity increase. This study putatively extends anammox bacterial habitats to extremely saline sulphidic ecosystems. 相似文献
63.
Environmental effects on population growth are often quantified by coupling environmental covariates with population time series, using statistical models that make particular assumptions about the shape of density dependence. We hypothesized that faulty assumptions about the shape of density dependence can bias estimated effect sizes of temporally autocorrelated covariates. We investigated the presence of bias using Monte Carlo simulations based on three common per capita growth functions with distinct density dependent forms (θ-Ricker, Ricker and Gompertz), autocorrelated (coloured) ‘known’ environmental covariates and uncorrelated (white) ‘unknown’ noise. Faulty assumptions about the shape of density dependence, combined with overcompensatory intrinsic population dynamics, can lead to strongly biased estimated effects of coloured covariates, associated with lower confidence interval coverage. Effects of negatively autocorrelated (blue) environmental covariates are overestimated, while those of positively autocorrelated (red) covariates can be underestimated, generally to a lesser extent. Prewhitening the focal environmental covariate effectively reduces the bias, at the expense of the estimate precision. Fitting models with flexible shapes of density dependence can also reduce bias, but increases model complexity and potentially introduces other problems of parameter identifiability. Model selection is a good option if an appropriate model is included in the set of candidate models. Under the specific and identifiable circumstances with high risk of bias, we recommend prewhitening or careful modelling of the shape of density dependence. 相似文献
64.
Two experiments were conducted to determine the establishment success of reintroducing Microlaena stipoides (pātītī, weeping rice grass) into existing high‐fertility grassland on the volcanic cones of the Auckland Isthmus. The first experiment monitored the survival and development of juveniles planted in a factorial design including two planting densities, two slope classes and two aspects across three cones. Plant survival during establishment was consistently over 90%. Maximum M. stipoides cover after 2 years (>80%) was achieved on north‐facing steep slopes (>25°) at the greater planting density (40 plants/m2). However, results were particularly idiosyncratic to specific cone/topographical combinations. The second experiment, on a flat site on one cone, monitored the survival and development of juveniles planted across four post‐planting treatments designed to suppress resident vegetation recovery. Plant survival after 6 months was relatively low (50%), and none of the treatments achieved greater than 5% cover of M. stipoides after 1 year. The chosen post‐planting treatments were unable to suppress vigorous recovery of competitive exotic grasses on a moist fertile site. Overall, juvenile planting was shown to be a potentially successful method of Microlaena establishment and could restore indigenous dominance to exotic grassland in this environment, but individual site factors and the high cost of establishment must be considered. 相似文献
65.
66.
Ahmed Hashim Toshiharu Abe Lijian Jin Yucheng Chang Zhi Chao Jin Jian Xun Sun George Hajishengallis Mike A. Curtis Richard P. Darveau 《Cellular microbiology》2013,15(8):1419-1426
The oral and intestinal host tissues both carry a heavy microbial burden. Although commensal bacteria contribute to healthy intestinal tissue structure and function, their contribution to oral health is poorly understood. A crucial component of periodontal health is the recruitment of neutrophils to periodontal tissue. To elucidate this process, gingival tissues of specific‐pathogen‐free and germ‐free wild‐type mice and CXCR2KO and MyD88KO mice were examined for quantitative analysis of neutrophils and CXCR2 chemoattractants (CXCL1, CXCL2). We show that the recruitment ofneutrophils to the gingival tissue does not require commensal bacterial colonization but is entirely dependent on CXCR2 expression. Strikingly, however, commensal bacteria selectively upregulate the expression of CXCL2, but not CXCL1, in a MyD88‐dependent way that correlates with increased neutrophil recruitment as compared with germ‐free conditions. This is the first evidence that the selective use of chemokine receptor ligands contributes to neutrophil homing to healthy periodontal tissue. 相似文献
67.
Tim Hendrikx Veerle Bieghs Sofie M. A. Walenbergh Patrick J. van Gorp Fons Verheyen Mike L. J. Jeurissen Mandy M. F. Steinbusch Nathalie Vaes Christoph J. Binder Ger H. Koek Rinke Stienstra Mihai G. Netea Marten H. Hofker Ronit Shiri-Sverdlov 《PloS one》2013,8(12)
Background & Aims
While non-alcoholic steatohepatitis (NASH) is characterized by hepatic steatosis combined with inflammation, the mechanisms triggering hepatic inflammation are unknown. In Ldlr-/- mice, we have previously shown that lysosomal cholesterol accumulation in Kupffer cells (KCs) correlates with hepatic inflammation and cholesterol crystallization. Previously, cholesterol crystals have been shown to induce the activation of inflammasomes. Inflammasomes are protein complexes that induce the processing and release of pro-inflammatory cytokines IL-1b and IL-18 via caspase-1 activation. Whereas caspase-1 activation is independent of caspase-11 in the canonical pathway of inflammasome activation, caspase-11 was found to trigger caspase-1-dependent IL-1b and IL-18 in response to non-canonical inflammasome activators. So far, it has not been investigated whether inflammasome activation stimulates the formation of cholesterol crystals. We hypothesized that inflammasome activation in KCs stimulates cholesterol crystallization, thereby leading to hepatic inflammation.Methods
Ldlr -/- mice were transplanted (tp) with wild-type (Wt) or caspase-1/11-/- (dKO) bone marrow and fed either regular chow or a high-fat, high-cholesterol (HFC) diet for 12 weeks. In vitro, bone marrow derived macrophages (BMDM) from wt or caspase-1/11-/- mice were incubated with oxLDL for 24h and autophagy was assessed.Results
In line with our hypothesis, caspase-1/11-/--tp mice had less severe hepatic inflammation than Wt-tp animals, as evident from liver histology and gene expression analysis in isolated KCs. Mechanistically, KCs from caspase-1/11-/--tp mice showed less cholesterol crystals, enhanced cholesterol efflux and increased autophagy. In wt BMDM, oxLDL incubation led to disturbed autophagy activity whereas BMDM from caspase-1/11-/- mice had normal autophagy activity.Conclusion
Altogether, these data suggest a vicious cycle whereby disturbed autophagy and decreased cholesterol efflux leads to newly formed cholesterol crystals and thereby maintain hepatic inflammation during NASH by further activating the inflammasome. 相似文献68.
Zaid A. Abassi Marina Okun-Gurevich Niroz Abu Salah Hoda Awad Yossi Mandel Gadi Campino Ahmad Mahajna Giora Z. Feuerstein Mike Fitzpatrick Aaron Hoffman Joseph Winaver 《PloS one》2013,8(11)
Uncontrolled hemorrhage, resulting from traumatic injuries, continues to be the leading cause of death in civilian and military environments. Hemorrhagic deaths usually occur within the first 6 hours of admission to hospital; therefore, early prehospital identification of patients who are at risk for developing shock may improve survival. The aims of the current study were: 1. To establish and characterize a unique model of uncontrolled internal hemorrhage induced by massive renal injury (MRI), of different degrees (20-35% unilateral nephrectomy) in rats, 2. To identify early biomarkers those best predict the outcome of severe internal hemorrhage. For this purpose, male Sprague Dawley rats were anesthetized and cannulas were inserted into the trachea and carotid artery. After abdominal laparotomy, the lower pole of the kidney was excised. During 120 minutes, hematocrit, pO2, pCO2, base excess, potassium, lactate and glucose were measured from blood samples, and mean arterial pressure (MAP) was measured through arterial tracing. After 120 minutes, blood loss was determined. Statistical prediction models of mortality and amount of blood loss were performed. In this model, the lowest blood loss and mortality rate were observed in the group with 20% nephrectomy. Escalation of the extent of nephrectomy to 25% and 30% significantly increased blood loss and mortality rate. Two phases of hemodynamic and biochemical response to MRI were noticed: the primary phase, occurring during the first 15 minutes after injury, and the secondary phase, beginning 30 minutes after the induction of bleeding. A Significant correlation between early blood loss and mean arterial pressure (MAP) decrements and survival were noted. Our data also indicate that prediction of outcome was attainable in the very early stages of blood loss, over the first 15 minutes after the injury, and that blood loss and MAP were the strongest predictors of mortality. 相似文献
69.
Mike F. Müller Simone Florian Stefanie Pommer Martin Osterhoff R. Steven Esworthy Fong-Fong Chu Regina Brigelius-Flohé Anna P. Kipp 《PloS one》2013,8(8)
The selenoprotein glutathione peroxidase-2 (GPx2) appears to have a dual role in carcinogenesis. While it protected mice from colon cancer in a model of inflammation-triggered carcinogenesis (azoxymethane and dextran sodium sulfate treatment), it promoted growth of xenografted tumor cells. Therefore, we analyzed the effect of GPx2 in a mouse model mimicking sporadic colorectal cancer (azoxymethane-treatment only). GPx2-knockout (KO) and wild-type (WT) mice were adjusted to an either marginally deficient (−Se), adequate (+Se), or supranutritional (++Se) selenium status and were treated six times with azoxymethane (AOM) to induce tumor development. In the −Se and ++Se groups, the number of tumors was significantly lower in GPx2-KO than in respective WT mice. On the +Se diet, the number of dysplastic crypts was reduced in GPx2-KO mice. This may be explained by more basal and AOM-induced apoptotic cell death in GPx2-KO mice that eliminates damaged or pre-malignant epithelial cells. In WT dysplastic crypts GPx2 was up-regulated in comparison to normal crypts which might be an attempt to suppress apoptosis. In contrast, in the +Se groups tumor numbers were similar in both genotypes but tumor size was larger in GPx2-KO mice. The latter was associated with an inflammatory and tumor-promoting environment as obvious from infiltrated inflammatory cells in the intestinal mucosa of GPx2-KO mice even without any treatment and characterized as low-grade inflammation. In WT mice the number of tumors tended to be lowest in +Se compared to −Se and ++Se feeding indicating that selenium might delay tumorigenesis only in the adequate status. In conclusion, the role of GPx2 and presumably also of selenium depends on the cancer stage and obviously on the involvement of inflammation. 相似文献
70.
Shaimaa Al-Janabi Henk-Jan van Slooten Mike Visser Tjeerd van der Ploeg Paul J. van Diest Mehdi Jiwa 《PloS one》2013,8(12)