全文获取类型
收费全文 | 714篇 |
免费 | 92篇 |
国内免费 | 1篇 |
出版年
2023年 | 7篇 |
2022年 | 13篇 |
2021年 | 23篇 |
2020年 | 6篇 |
2019年 | 12篇 |
2018年 | 20篇 |
2017年 | 15篇 |
2016年 | 27篇 |
2015年 | 54篇 |
2014年 | 50篇 |
2013年 | 56篇 |
2012年 | 66篇 |
2011年 | 58篇 |
2010年 | 27篇 |
2009年 | 36篇 |
2008年 | 40篇 |
2007年 | 44篇 |
2006年 | 45篇 |
2005年 | 34篇 |
2004年 | 42篇 |
2003年 | 32篇 |
2002年 | 25篇 |
2001年 | 6篇 |
2000年 | 2篇 |
1999年 | 10篇 |
1998年 | 8篇 |
1997年 | 5篇 |
1996年 | 3篇 |
1995年 | 5篇 |
1994年 | 6篇 |
1993年 | 3篇 |
1992年 | 3篇 |
1991年 | 2篇 |
1990年 | 3篇 |
1989年 | 1篇 |
1988年 | 1篇 |
1987年 | 2篇 |
1985年 | 3篇 |
1984年 | 4篇 |
1983年 | 2篇 |
1982年 | 2篇 |
1978年 | 1篇 |
1971年 | 1篇 |
1956年 | 1篇 |
1949年 | 1篇 |
排序方式: 共有807条查询结果,搜索用时 31 毫秒
51.
Ling?HuangEmail author Anton?W.?Langerak Ingrid?L.?M.?Wolvers-Tettero Ruud?W.?J.?Meijers Carla?C.?Baan Nicolle?H.?R.?Litjens Michiel?G.?H.?Betjes 《Immunity & ageing : I & A》2015,12(1):28
Background
End stage renal disease (ESRD) is associated with defective T-cell mediated immunity. A diverse T-cell receptor (TCR) Vβ repertoire is central to effective T-cell mediated immune responses to foreign antigens. In this study, the effect of ESRD on TCR Vβ repertoire was assessed.Results
A higher proportion of ESRD patients (68.9 %) had a skewed TCR Vβ repertoire compared to age and cytomegalovirus (CMV) – IgG serostatus matched healthy individuals (31.4 %, P?<?0.001). Age, CMV serostatus and ESRD were independently associated with an increase in shifting of the TCR Vβ repertoire. More differentiated CD8+ T cells were observed in young ESRD patients with a shifted TCR Vβ repertoire. CD31-expressing naive T cells and relative telomere length of T cells were not significantly related to TCR Vβ skewing.Conclusions
ESRD significantly skewed the TCR Vβ repertoire particularly in the elderly population, which may contribute to the uremia-associated defect in T-cell mediated immunity.52.
Claire H. den Hoedt Muriel P. C. Grooteman Michiel L. Bots Peter J. Blankestijn Ingeborg van der Tweel Neelke C. van der Weerd E. Lars Penne Albert H. A. Mazairac Renée Levesque Piet M. ter Wee Menso J. Nubé Marinus A. van den Dorpel CONTRAST investigators 《PloS one》2015,10(8)
Background
Hemodialysis (HD) patients have a high risk of infections. The uremic milieu has a negative impact on several immune responses. Online hemodiafiltration (HDF) may reduce the risk of infections by ameliorating the uremic milieu through enhanced clearance of middle molecules. Since there are few data on infectious outcomes in HDF, we compared the effects of HDF with low-flux HD on the incidence and type of infections.Patients and Methods
We used data of the 714 HD patients (age 64 ±14, 62% men, 25% Diabetes Mellitus, 7% catheters) participating in the CONvective TRAnsport STudy (CONTRAST), a randomized controlled trial evaluating the effect of HDF as compared to low-flux HD. The events were adjudicated by an independent event committee. The risk of infectious events was compared with Cox regression for repeated events and Cox proportional hazard models. The distributions of types of infection were compared between the groups.Results
Thirty one percent of the patients suffered from one or more infections leading to hospitalization during the study (median follow-up 1.96 years). The risk for infections during the entire follow-up did not differ significantly between treatment arms (HDF 198 and HD 169 infections in 800 and 798 person-years respectively, hazard ratio HDF vs. HD 1.09 (0.88–1.34), P = 0.42. No difference was found in the occurrence of the first infectious event (either fatal, non-fatal or type specific). Of all infections, respiratory infections (25% in HDF, 28% in HD) were most common, followed by skin/musculoskeletal infections (21% in HDF, 13% in HD).Conclusions
HDF as compared to HD did not result in a reduced risk of infections, larger studies are needed to confirm our findings.Trial Registration
ClinicalTrials.gov NCT00205556 相似文献53.
54.
55.
Gijs Fortrie Susanne Stads Albert-Jan H. Aarnoudse Robert Zietse Michiel G. Betjes 《PloS one》2015,10(3)
Background and Objectives
Acute kidney injury (AKI) necessitating renal replacement therapy (RRT) is associated with high mortality and increased risk for end stage renal disease. However, it is unknown if this applies to patients with a preliminary unremarkable medical history. The purpose of this study was to describe overall and renal survival in critically ill patients with AKI necessitating RRT stratified by the presence of comorbidity.Design, Setting, Participants, and Measurements
A retrospective cohort study was performed, between 1994 and 2010, including all adult critically ill patients with AKI necessitating RRT, stratified by the presence of comorbidity. Logistic regression, survival curve and cox proportional hazards analyses were used to evaluate overall and renal survival. Standardized mortality rate (SMR) analysis was performed to compare long-term survival to the predicted survival in the Dutch population.Results
Of the 1067 patients included only 96(9.0%) had no comorbidity. Hospital mortality was 56.6% versus 43.8% in patients with and without comorbidity, respectively. In those who survived hospitalization 10-year survival was 45.0% and 86.0%, respectively. Adjusted for age, sex and year of treatment, absence of comorbidity was not associated with hospital mortality (OR=0.74, 95%-CI=0.47-1.15), while absence of comorbidity was associated with better long-term survival (adjusted HR=0.28, 95%-CI = 0.14-0.58). Compared to the Dutch population, patients without comorbidity had a similar mortality risk (SMR=1.6, 95%-CI=0.7-3.2), while this was increased in patients with comorbidity (SMR=4.8, 95%-CI=4.1-5.5). Regarding chronic dialysis dependency, 10-year renal survival rates were 76.0% and 92.9% in patients with and without comorbidity, respectively. Absence of comorbidity was associated with better renal survival (adjusted HR=0.24, 95%-CI=0.07-0.76).Conclusions
While hospital mortality remains excessively high, the absence of comorbidity in critically ill patients with RRT-requiring AKI is associated with a relative good long-term prognosis in those who survive hospitalization. 相似文献56.
Ecological Risk Assessment of a Metal-Contaminated Area in the Tropics. Tier II: Detailed Assessment
Júlia Carina Niemeyer Matilde Moreira-Santos Rui Ribeiro Michiel Rutgers Marco Antonio Nogueira Eduardo Mendes da Silva José Paulo Sousa 《PloS one》2015,10(11)
This study presents data on the detailed evaluation (tier 2) of a site-specific ecological risk assessment (ssERA) in a former smelter area contaminated with metals (Santo Amaro, Bahia, Brazil). Combining information from three lines of evidence (LoE), chemical (ChemLoE), ecotoxicological (EcotoxLoE) and ecological (EcoLoE), in the Triad approach, integrated risk values were calculated to rank sites and confirm the potential risk disclosed with tier 1. Risk values were calculated for the habitat and for the retention functions in each sampling point. Habitat function included the ChemLoE calculated from total metal concentrations. The EcotoxLoE was based on reproduction tests with terrestrial invertebrates (Folsomia candida, Enchytraeus crypticus, Eisenia andrei), shoot length and plant biomass (Avena sativa, Brassica rapa). For the EcoLoE, ecological parameters (microbial parameters, soil invertebrate community, litter breakdown) were used to derive risk values. Retention function included the ChemLoE, calculated from extractable metal concentrations, and the EcotoxLoE based on eluate tests with aquatic organisms (Daphnia magna reproduction and Pseudokirchneriella subcapitata growth). Results related to the habitat function indicated that the metal residues are sufficient to cause risk to biota, while the low metal levels in extracts and the general lack of toxicity in aquatic tests indicated a high soil retention capacity in most sampling points. Integrated risk of tier 2 showed the same trend of tier 1, suggesting the need to proceed with remediation actions. The high risk levels were related to direct toxicity to organisms and indirect effects, such as failure in the establishment of vegetation and the consequent loss of habitat quality for microorganisms and soil fauna. This study shed some light on the selection of tools for the tier 2 of an ssERA in tropical metal-contaminated sites, focusing on ecological receptors at risk and using available chemical methods, ecological surveys and ecotoxicity tests. 相似文献
57.
Camiel L. M. de Roij van Zuijdewijn Muriel P. C. Grooteman Michiel L. Bots Peter J. Blankestijn Sonja Steppan Janine Büchel Rolf H. H. Groenwold Vincent Brandenburg Marinus A. van den Dorpel Piet M. ter Wee Menso J. Nubé Marc G. Vervloet 《PloS one》2015,10(11)
Despite suggestions that higher serum magnesium (Mg) levels are associated with improved outcome, the association with mortality in European hemodialysis (HD) patients has only scarcely been investigated. Furthermore, data on the association between serum Mg and sudden death in this patient group is limited. Therefore, we evaluated Mg in a post-hoc analysis using pooled data from the CONvective TRAnsport STudy (CONTRAST, NCT00205556), a randomized controlled trial (RCT) evaluating the survival risk in dialysis patients on hemodiafiltration (HDF) compared to HD with a mean follow-up of 3.1 years. Serum Mg was measured at baseline and 6, 12, 24 and 36 months thereafter. Cox proportional hazards models, adjusted for confounders using inverse probability weighting, were used to estimate hazard ratios (HRs) of baseline serum Mg on all-cause mortality, cardiovascular mortality, non-cardiovascular mortality and sudden death. A generalized linear mixed model was used to investigate Mg levels over time. Out of 714 randomized patients, a representative subset of 365 (51%) were analyzed in the present study. For every increase in baseline serum Mg of 0.1 mmol/L, the HR for all-cause mortality was 0.85 (95% CI 0.77–94), the HR for cardiovascular mortality 0.73 (95% CI 0.62–0.85) and for sudden death 0.76 (95% CI 0.62–0.93). These findings did not alter after extensive correction for potential confounders, including treatment modality. Importantly, no interaction was found between serum phosphate and serum Mg. Baseline serum Mg was not related to non-cardiovascular mortality. Mg decreased slightly but statistically significant over time (Δ -0.011 mmol/L/year, 95% CI -0.017 to -0.009, p = 0.03). In short, serum Mg has a strong, independent association with all-cause mortality, cardiovascular mortality and sudden death in European HD patients. Serum Mg levels decrease slightly over time. 相似文献
58.
Bart B. L. Groen Astrid M. Horstman Henrike M. Hamer Michiel de Haan Janneau van Kranenburg J?rgen Bierau Martijn Poeze Will K. W. H. Wodzig Blake B. Rasmussen Luc J. C. van Loon 《PloS one》2015,10(11)
Background
Protein turnover in skeletal muscle tissue is highly responsive to nutrient intake in healthy adults.Objective
To provide a comprehensive overview of post-prandial protein handling, ranging from dietary protein digestion and amino acid absorption, the uptake of dietary protein derived amino acids over the leg, the post-prandial stimulation of muscle protein synthesis rates, to the incorporation of dietary protein derived amino acids in de novo muscle protein.Design
12 healthy young males ingested 20 g intrinsically [1-13C]-phenylalanine labeled protein. In addition, primed continuous L-[ring-2H5]-phenylalanine, L-[ring-2H2]-tyrosine, and L-[1-13C]-leucine infusions were applied, with frequent collection of arterial and venous blood samples, and muscle biopsies throughout a 5 h post-prandial period. Dietary protein digestion, amino acid absorption, splanchnic amino acid extraction, amino acid uptake over the leg, and subsequent muscle protein synthesis were measured within a single in vivo human experiment.Results
55.3±2.7% of the protein-derived phenylalanine was released in the circulation during the 5 h post-prandial period. The post-prandial rise in plasma essential amino acid availability improved leg muscle protein balance (from -291±72 to 103±66 μM·min-1·100 mL leg volume-1; P<0.001). Muscle protein synthesis rates increased significantly following protein ingestion (0.029±0.002 vs 0.044±0.004%·h-1 based upon the muscle protein bound L-[ring-2H5]-phenylalanine enrichments (P<0.01)), with substantial incorporation of dietary protein derived L-[1-13C]-phenylalanine into de novo muscle protein (from 0 to 0.0201±0.0025 MPE).Conclusion
Ingestion of a single meal-like amount of protein allows ~55% of the protein derived amino acids to become available in the circulation, thereby improving whole-body and leg protein balance. About 20% of the dietary protein derived amino acids released in the circulation are taken up in skeletal muscle tissue following protein ingestion, thereby stimulating muscle protein synthesis rates and providing precursors for de novo muscle protein synthesis.Trial Registration
trialregister.nl 3638 相似文献59.
Justin V. Joseph Ingrid A. M. van Roosmalen Ellen Busschers Tushar Tomar Siobhan Conroy Ellie Eggens-Meijer Natalia Pe?aranda Fajardo Milind M. Pore Veerakumar Balasubramanyian Michiel Wagemakers Sjef Copray Wilfred F. A. den Dunnen Frank A. E. Kruyt 《PloS one》2015,10(12)
Glioblastoma (GBM) is a highly infiltrative brain tumor in which cells with properties of stem cells, called glioblastoma stem cells (GSCs), have been identified. In general, the dominant view is that GSCs are responsible for the initiation, progression, invasion and recurrence of this tumor. In this study, we addressed the question whether the differentiation status of GBM cells is associated with their invasive capacity. For this, several primary GBM cell lines were used, cultured either as neurospheres known to enrich for GSCs or in medium supplemented with 10% FCS that promotes differentiation. The differentiation state of the cells was confirmed by determining the expression of stem cell and differentiation markers. The migration/invasion potential of these cells was tested using in vitro assays and intracranial mouse models. Interestingly, we found that serum-induced differentiation enhanced the invasive potential of GBM cells, which was associated with enhanced MMP9 expression. Chemical inhibition of MMP9 significantly reduced the invasive potential of differentiated cells in vitro. Furthermore, the serum-differentiated cells could revert back to an undifferentiated/stem cell state that were able to form neurospheres, although with a reduced efficiency as compared to non-differentiated counterparts. We propose a model in which activation of the differentiation program in GBM cells enhances their infiltrative potential and that depending on microenvironmental cues a significant portion of these cells are able to revert back to an undifferentiated state with enhanced tumorigenic potential. Thus, effective therapy should target both GSCs and differentiated offspring and targeting of differentiation-associated pathways may offer therapeutic opportunities to reduce invasive growth of GBM. 相似文献
60.
Michiel van Elk 《PloS one》2015,10(6)
Previous studies have shown that one’s prior beliefs have a strong effect on perceptual decision-making and attentional processing. The present study extends these findings by investigating how individual differences in paranormal and conspiracy beliefs are related to perceptual and attentional biases. Two field studies were conducted in which visitors of a paranormal conducted a perceptual decision making task (i.e. the face / house categorization task; Experiment 1) or a visual attention task (i.e. the global / local processing task; Experiment 2). In the first experiment it was found that skeptics compared to believers more often incorrectly categorized ambiguous face stimuli as representing a house, indicating that disbelief rather than belief in the paranormal is driving the bias observed for the categorization of ambiguous stimuli. In the second experiment, it was found that skeptics showed a classical ‘global-to-local’ interference effect, whereas believers in conspiracy theories were characterized by a stronger ‘local-to-global interference effect’. The present study shows that individual differences in paranormal and conspiracy beliefs are associated with perceptual and attentional biases, thereby extending the growing body of work in this field indicating effects of cultural learning on basic perceptual processes. 相似文献