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961.
Marianne van der Mark Peter C. G. Nijssen Jelle Vlaanderen Anke Huss Wim M. Mulleners Antonetta M. G. Sas Teus van Laar Hans Kromhout Roel Vermeulen 《PloS one》2014,9(4)
The aim of this study was to investigate the possible reduced risk of Parkinson Disease (PD) due to coffee, alcohol, and/or cigarette consumption. In addition, we explored the potential effect modification by intensity, duration and time-since-cessation of smoking on the association between cumulative pack-years of cigarette smoking (total smoking) and PD risk. Data of a hospital based case-control study was used including 444 PD patients, diagnosed between 2006 and 2011, and 876 matched controls from 5 hospitals in the Netherlands. A novel modeling method was applied to derive unbiased estimates of the potential modifying effects of smoking intensity, duration, and time-since-cessation by conditioning on total exposure. We observed no reduced risk of PD by alcohol consumption and only a weak inverse association between coffee consumption and PD risk. However, a strong inverse association of total smoking with PD risk was observed (OR = 0.27 (95%CI: 0.18–0.42) for never smokers versus highest quartile of tobacco use). The observed protective effect of total smoking was significantly modified by time-since-cessation with a diminishing protective effect after cessation of smoking. No effect modification by intensity or duration of smoking was observed indicating that both intensity and duration have an equal contribution to the reduced PD risk. Understanding the dynamics of the protective effect of smoking on PD risk aids in understanding PD etiology and may contribute to strategies for prevention and treatment. 相似文献
962.
Rawiah Alsiary Anke Brüning-Richardson Jacquelyn Bond Ewan E. Morrison Nafisa Wilkinson Sandra M. Bell 《PloS one》2014,9(5)
Mutations in the MCPH1 (Microcephalin) and ASPM (abnormal spindle-like microcephaly associated) genes cause primary microcephaly. Both are centrosomal associated proteins involved in mitosis. Microcephalin plays an important role in DNA damage response and ASPM is required for correct division of proliferative neuro-epithelial cells of the developing brain. Reduced MCPH1 mRNA expression and ASPM mRNA over-expression have been implicated in the development of human carcinomas. Epithelial ovarian cancer (EOC) is characterised by highly aneuploid tumours. Previously we have reported low Microcephalin and high ASPM protein levels and associations with clinico-pathological parameters in malignant cells from ascitic fluids. To confirm these previous findings on a larger scale Microcephalin and ASPM expression levels and localisations were evaluated by immunohistochemistry in two cohorts; a training set of 25 samples and a validation set of 322 EOC tissue samples. Results were correlated to the associated histopathological data. In normal ovarian tissues the Microcephalin nuclear staining pattern was consistently strong. In the cancer tissues, we identified low nuclear Microcephalin expression in high grade and advanced stage tumours (p<0.0001 and p = 0.0438 respectively). ASPM had moderate to high nuclear and low to moderate cytoplasmic expression in normal tissue. Cytoplasmic ASPM expression decreased with tumour grade and stage in the serous subtype of EOC (p = 0.023 and p = 0.011 respectively). Cytoplasmic ASPM increased with tumour stage in the endometrioid subtype (p = 0.023). Increasing tumour invasiveness (T3) and lymph node involvement (N1) also correlated with a decrease in cytoplasmic ASPM in EOC (p = 0.02 and p = 0.04 respectively). We have validated previous findings of deregulated expression of Microcephalin and ASPM in EOC by confirming associations for low nuclear Microcephalin levels and high cytoplasmic ASPM levels in a larger scale tumour tissue study. Microcephalin and ASPM may prove useful biomarkers in EOC. 相似文献
963.
Background
An evidence-based approach to health care is recognized internationally as a key competency for healthcare practitioners. This overview systematically evaluated and organized evidence from systematic reviews on teaching evidence-based health care (EBHC).Methods/Findings
We searched for systematic reviews evaluating interventions for teaching EBHC to health professionals compared to no intervention or different strategies. Outcomes covered EBHC knowledge, skills, attitudes, practices and health outcomes. Comprehensive searches were conducted in April 2013. Two reviewers independently selected eligible reviews, extracted data and evaluated methodological quality. We included 16 systematic reviews, published between 1993 and 2013. There was considerable overlap across reviews. We found that 171 source studies included in the reviews related to 81 separate studies, of which 37 are in more than one review. Studies used various methodologies to evaluate educational interventions of varying content, format and duration in undergraduates, interns, residents and practicing health professionals. The evidence in the reviews showed that multifaceted, clinically integrated interventions, with assessment, led to improvements in knowledge, skills and attitudes. Interventions improved critical appraisal skills and integration of results into decisions, and improved knowledge, skills, attitudes and behaviour amongst practicing health professionals. Considering single interventions, EBHC knowledge and attitude were similar for lecture-based versus online teaching. Journal clubs appeared to increase clinical epidemiology and biostatistics knowledge and reading behavior, but not appraisal skills. EBHC courses improved appraisal skills and knowledge. Amongst practicing health professionals, interactive online courses with guided critical appraisal showed significant increase in knowledge and appraisal skills. A short workshop using problem-based approaches, compared to no intervention, increased knowledge but not appraisal skills.Conclusions
EBHC teaching and learning strategies should focus on implementing multifaceted, clinically integrated approaches with assessment. Future rigorous research should evaluate minimum components for multifaceted interventions, assessment of medium to long-term outcomes, and implementation of these interventions. 相似文献964.
Jana Burkhardt Mechthild Blume Elisabeth Petit-Teixeira Vitor Hugo Teixeira Anke Steiner Elfi Quente Grit Wolfram Markus Scholz Céline Pierlot Paola Migliorini Stefano Bombardieri Alejandro Balsa René Westhovens Pilar Barrera Timothy R. D. J. Radstake Helena Alves Thomas Bardin Bernard Prum Frank Emmrich Fran?ois Cornelis Peter Ahnert Holger Kirsten 《PloS one》2014,9(8)
965.
DHPLC mutation analysis of the hereditary nonpolyposis colon cancer (HNPCC) genes hMLH1 and hMSH2 总被引:9,自引:0,他引:9
Holinski-Feder E Müller-Koch Y Friedl W Moeslein G Keller G Plaschke J Ballhausen W Gross M Baldwin-Jedele K Jungck M Mangold E Vogelsang H Schackert HK Lohsea P Murken J Meitinger T 《Journal of biochemical and biophysical methods》2001,47(1-2):21-32
Denaturing high-performance liquid chromatography (DHPLC) is an efficient method for detection of mutations involving a single or few numbers of nucleotides, and it has been successfully used for mutation detection in disease-related genes. Colorectal cancer is one of the most common cancers, and mutations in the genes for hereditary nonpolyposis colon cancer (HNPCC), hMLH1 and hMSH2, also involve mainly point mutations. Sequence analysis is supposed to be a screening method with high sensitivity; however, it is time-consuming and expensive. We therefore decided to test sensitivity and reproducibility of DHPLC for 71 sequence variants in hMLH1 and hMSH2 initially found by sequence analysis in DNA samples of German HNPCC patients. DHPLC conditions of the PCR products were based on the melting pattern of the wild-type sequence of the corresponding PCR fragments. All but one of the 71 mutations was detected using DHPLC (sensitivity of 97%). Running time per sample averaged only 7 min, and the system is highly automated. Thus DHPLC is a rapid and sensitive method for the detection of hMLH1 and hMSH2 sequence variants. 相似文献
966.
Burmester A Shelest E Glöckner G Heddergott C Schindler S Staib P Heidel A Felder M Petzold A Szafranski K Feuermann M Pedruzzi I Priebe S Groth M Winkler R Li W Kniemeyer O Schroeckh V Hertweck C Hube B White TC Platzer M Guthke R Heitman J Wöstemeyer J Zipfel PF Monod M Brakhage AA 《Genome biology》2011,12(1):R7-16
967.
Günther T Schmitt AO Bortfeldt RH Hinney A Hebebrand J Brockmann GA 《Omics : a journal of integrative biology》2011,15(7-8):507-512
Recent technological progress has permitted the efficient performance of genome-wide association studies (GWAS) to map genetic variants associated with common diseases. Here, we analyzed 2,893 single nucleotide polymorphisms (SNPs) that have been identified in 593 published GWAS as associated with a disease phenotype with respect to their genomic location. In absolute numbers, most significant SNPs are located in intergenic regions and introns. When compared to their representation on the chips, there is essentially overrepresentation of nonsynonymous coding SNPs (nsSNPs), synonymous coding SNPs, and SNPs in untranscribed regions upstream of genes among the disease associated SNPs. A Gene Ontology term analysis showed that genes putatively causing a phenotype often code for membrane associated proteins or signal transduction genes. 相似文献
968.
Francis Orata Anke Maes Friedrich Werres Rolf Dieter Wilken 《Soil & Sediment Contamination》2011,20(2):129-141
Perfluorooctanoic acid and perfluorooctane sulfonate were determined in the sediments from Winam Gulf, which is in the Kenyan side of Lake Victoria and in its source rivers. The sources of perfluorinated compounds within the Gulf of Lake Victoria have been identified and their levels determined for the first time, in this study, using SPE and HPLC-MS-MS analytical methodology. Variability in the concentrations of perfluorooctanoic acid and perfluorooctane sulfonate ranged from 1.4–99.1 and <1–57.5 ng/g in river sediments, respectively, which was higher than concentrations obtained from lake sediments (range perfluorooctanoic acid <1–24.1 ng/g and perfluorooctane sulfonate <1–4.0 ng/g). The results obtained suggested generalized point sources such as domestic and industrial waste indicated by significant correlation and regression of r2 = 0.857. Sampling sites within and near sewage and water treatment facilities gave the highest concentrations of both analytes, and were observed to be the main source of perfluorinated compounds pollution. The lowest limit of quantification was 1 ng/g for both analytes and limits of detection were 0.1 and 0.2 ng/g for perfluorooctanoic acid and perfluorooctane sulfonate, respectively. Typical values for recovery obtained were higher than 78% from spiked amounts ranging from 1 to 150 ng. Quantifying perfluoro alkylated compounds in sediments have provided insights into their source, distribution, and mobility in the Lake Victoria Basin. 相似文献
969.
van Oorschot AA Smits AM Pardali E Doevendans PA Goumans MJ 《Journal of cellular and molecular medicine》2011,15(12):2723-2734
Previously we observed that cardiomyocyte progenitor cells (hCMPCs) isolated from the human heart differentiate spontaneously into cardiomyocytes and vascular cells when transplanted after myocardial infarction (MI) in the ischemic heart. After MI, deprivation of oxygen is the first major change in the cardiac environment. How cells handle hypoxia is highly cell type dependent. The effect of hypoxia on cardiac stem or progenitor cells remains to be elucidated. Here, we show for the first time that short- and long-term hypoxia have different effects on hCMPCs. Short-term hypoxia increased the migratory and invasive capacities of hCMPCs likely via mesenchymal transformation. Although long-term exposure to low oxygen levels did not induce differentiation of hCMPCs into mature cardiomyocytes or endothelial cells, it did increase their proliferation, stimulated the secretome of the cells which was shifted to a more anti-inflammatory profile and dampened the migration by altering matrix metalloproteinase (MMP) modulators. Interestingly, hypoxia greatly induced the expression of the extracellular matrix modulator thrombospondin-2 (TSP-2). Knockdown of TSP-2 resulted in increased proliferation, migration and MMP activity. In conclusion, short exposure to hypoxia increases migratory and invasive capacities of hCMPCs and prolonged exposure induces proliferation, an angiogenic secretion profile and dampens migration, likely controlled by TSP-2. 相似文献
970.