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991.
Matthias M. Gaida Thomas Große Steffen Frank Günther Darjus F. Tschaharganeh Klaus Felix Frank Bergmann Peter Schirmacher Gertrud M. Hänsch 《European journal of immunology》2012,42(12):3369-3380
Pancreatic ductal adenocarcinoma (PDAC) presenting with a micropapillary growth pattern is frequently associated with a prominent neutrophil infiltration into the tumor. The relevance of neutrophil infiltrates for tumor progression, however, is still debated. To gain insight into the role of polymorphonuclear neutrophils (PMNs) in PDAC, we assessed their effect on pancreatic tumor cells grown in vitro as monolayers. Time‐lapse video microscopy showed a PMN‐induced dyshesion of the tumor cells, and subsequent experiments revealed that this dyshesion was due to PMN elastase‐mediated degradation of E‐cadherin, an adhesion molecule that mediates the intercellular contact of the tumor cells. E‐cadherin degradation by elastase or — (for comparison) down‐modulation by specific siRNA, significantly increased the migratory capacity of the pancreatic tumor cells, leading to the hypothesis that PMNs could contribute to the invasive tumor growth. To address this issue, biopsies of patients with PDAC (n = 112) were analyzed. We found that E‐cadherin expression correlated negatively with PMN infiltration, compatible with the notion that E‐cadherin is cleaved by PMN‐derived elastase, which in turn could result in the dispersal of the tumor cells, enhanced migratory capacity and thus invasive tumor growth. 相似文献
992.
Donlin LT Andresen C Just S Rudensky E Pappas CT Kruger M Jacobs EY Unger A Zieseniss A Dobenecker MW Voelkel T Chait BT Gregorio CC Rottbauer W Tarakhovsky A Linke WA 《Genes & development》2012,26(2):114-119
Protein lysine methylation is one of the most widespread post-translational modifications in the nuclei of eukaryotic cells. Methylated lysines on histones and nonhistone proteins promote the formation of protein complexes that control gene expression and DNA replication and repair. In the cytoplasm, however, the role of lysine methylation in protein complex formation is not well established. Here we report that the cytoplasmic protein chaperone Hsp90 is methylated by the lysine methyltransferase Smyd2 in various cell types. In muscle, Hsp90 methylation contributes to the formation of a protein complex containing Smyd2, Hsp90, and the sarcomeric protein titin. Deficiency in Smyd2 results in the loss of Hsp90 methylation, impaired titin stability, and altered muscle function. Collectively, our data reveal a cytoplasmic protein network that employs lysine methylation for the maintenance and function of skeletal muscle. 相似文献
993.
MS Bojer AM Hammerum SL Jørgensen F Hansen SS Olsen KA Krogfelt C Struve 《APMIS : acta pathologica, microbiologica, et immunologica Scandinavica》2012,120(9):699-705
A plasmid-encoded ClpK protein was recently identified as a predictor of a heat-resistant phenotype in the opportunistic pathogen Klebsiella pneumoniae. This study was undertaken to evaluate the presence of the clpK gene in extended-spectrum β-lactamase (ESBL)-producing K. pneumoniae and to assess the probable co-transfer of multi-resistance with the heat resistance phenotype. A Danish collection of 80 ESBL-producing K. pneumoniae bloodstream infection isolates was screened for clpK by colony hybridization. Nineteen isolates (24%) were positive for clpK; some of them representing major clones identified in Denmark. Among these, nine isolates belonged to a single K. pneumoniae CTX-M-15 clone with sequence type (ST)16 exhibiting a heat-resistant phenotype. This clone has a multi-hospital occurrence and has also been detected outside Denmark. Horizontal co-transfer of multiple antibiotic resistances, including the CTX-M-15 resistance determinant, and the heat resistance phenotype was observed. Thus, the clpK gene is harbored by different ESBL-producing K. pneumoniae isolates including a clone of ST16 internationally spread. The co-localization of clpK on transferable ESBL-encoding plasmids allowing co-dissemination of multiple drug resistance with bacterial heat resistance is a highly interesting phenomenon that may further complicate the prevention of spreading of certain successful clones of multi-resistant K. pneumoniae. 相似文献
994.
995.
996.
Harnack LJ Steffen L Zhou X Luepker RV 《Journal of the American Dietetic Association》2011,111(9):1329-1334
Background
Changes in eating habits could potentially be contributing to vitamin D insufficiency among US adults.Objective
Describe secular trends in vitamin D intake from food sources during the past 25 years.Design
Trends in dietary vitamin D intake from 1980-1982 to 2007-2009 were examined using data collected from the Minnesota Heart Survey, a surveillance study of trends in risk factors for cardiovascular disease among probability samples of adults aged 25 to 74 years in the Minneapolis-St Paul, MN, metropolitan area. Surveys were conducted in 1980-1982, 1985-1987, 1990-1992, 1995-1997, 2000-2002, and 2007-2009. One 24-hour recall was collected from survey participants during each survey period.Results
Vitamin D intake from food sources decreased between 1980-1982 and 2007-2009 among men, with age-adjusted mean vitamin D intake decreasing from 7.24 μg/day in 1980-1982 to 6.15 μg/day in 2007-2009 (P for trend <0.001). A decrease was also observed among women (4.77 μg/day in 1980-1982 in comparison to 4.53 μg/day in 2007-2009; P for trend <0.001).Conclusions
Results suggest that vitamin D intake from food sources has been on the decline during the past 25 years among men and women, potentially contributing to vitamin D insufficiency. 相似文献997.
Kristensen DM Skalkam ML Audouze K Lesné L Desdoits-Lethimonier C Frederiksen H Brunak S Skakkebæk NE Jégou B Hansen JB Junker S Leffers H 《Environmental health perspectives》2011,119(4):534-541
Background
Prostaglandins (PGs) play key roles in development and maintenance of homeostasis of the adult body. Despite these important roles, it remains unclear whether the PG pathway is a target for endocrine disruption. However, several known endocrine-disrupting compounds (EDCs) share a high degree of structural similarity with mild analgesics.Objectives and Methods
Using cell-based transfection and transduction experiments, mass spectrometry, and organotypic assays together with molecular modeling, we investigated whether inhibition of the PG pathway by known EDCs could be a novel point of endocrine disruption.Results
We found that many known EDCs inhibit the PG pathway in a mouse Sertoli cell line and in human primary mast cells. The EDCs also reduced PG synthesis in ex vivo rat testis, and this reduction was correlated with a reduced testosterone production. The inhibition of PG synthesis occurred without involvement of canonical PG receptors or the peroxisome proliferator–activated receptors (PPARs), which have previously been described as targets of EDCs. Instead, our results suggest that the compounds may bind directly into the active site of the cyclooxygenase (COX) enzymes, thereby obstructing the conversion of arachidonic acid to PG precursors without interfering with the expression of the COX enzymes. A common feature of the PG inhibitory EDCs is the presence of aromatic groups that may stabilize binding in the hydrophobic active site of the COX enzymes.Conclusion
Our findings suggest a hitherto unknown mode of action by EDCs through inhibition of the PG pathway and suggest new avenues to investigate effects of EDCs on reproductive and immunological disorders that have become increasingly common in recent decades. 相似文献998.
999.
1000.
Hussmann B Lefering R Waydhas C Ruchholtz S Wafaisade A Kauther MD Lendemans S 《Critical care (London, England)》2011,15(5):R207