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Evaluation of training nurses to perform semi‐automated three‐dimensional left ventricular ejection fraction using a customised workstation‐based training protocol 下载免费PDF全文
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Parminder Suchdev Kym Ahrens Eleanor Click Lori Macklin Doris Evangelista Elinor Graham 《Ambulatory Pediatrics》2007,7(4):317-320
The health status of many people in developing countries is often dismal compared with the norms in industrialized countries. Increasingly, medical practitioners in the United States and other industrialized countries have become interested in global health issues, an interest that often takes the form of short-term international medical trips. We discuss several ethical issues associated with participation in such trips and use our experiences in developing the Children's Health International Medical Project of Seattle (CHIMPS) to outline and illustrate a set of 7 guiding principles for making these trips. CHIMPS is a resident-run, faculty-supported international medical program founded in 2002 by pediatric residents at the University of Washington in Seattle. Members of CHIMPS work with a rural community in El Salvador to support ongoing public health interventions there and provide sustainable medical care in collaboration with the community and a local nongovernmental organization. The 7 principles developed as a result of this work-mission, collaboration, education, service, teamwork, sustainability, and evaluation-can be used as a model for health practitioners as they develop or select international medical trips. The importance of partnering with the community and working within the existing medical and public health infrastructure is emphasized. Many of the challenges of doing international medical work can be overcome when efforts are guided by a few specific principles, such as those we have outlined. 相似文献
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Between 1996 and 1998, two clades (B and C; genotype I) of dengue virus type 1 (DENV-1) appeared in Myanmar (Burma) that were new to that location. Between 1998 and 2000, a third clade (A; genotype III) of DENV-1, which had been circulating at that locality for at least 25 years, became extinct. These changes preceded the largest outbreak of dengue recorded in Myanmar, in 2001, in which more than 95% of viruses recovered from patients were DENV-1, but where the incidence of severe disease was much less than in previous years. Phylogenetic analyses of viral genomes indicated that the two new clades of DENV-1 did not arise from the, now extinct, clade A viruses nor was the extinction of this clade due to differences in the fitness of the viral populations. Since the extinction occurred during an inter-epidemic period, we suggest that it was due to a stochastic event attributable to the low rate of virus transmission in this interval. 相似文献
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Olof Beck Kym F. Faull David B. Repke 《Naunyn-Schmiedeberg's archives of pharmacology》1986,333(3):307-312
Summary Racemic methtryptoline (1-methyltetrahydro--carboline) and 5-hydroxymethtryptoline-9-carboxylic acid (6-hydroxy-1-methyltetrahydro--carboline-1-carboxylic acid) were administered intraperitoneally to rats and the components of their urine was subsequently investigated by chiral gas chromatography-mass spectrometry. Methtryptoline rapidly became hydroxylated in the 5- and 6-position and excreted in urine. There was about a ninefold predominance of the S(–) enantiomer over the other in the 5-hydroxylated species, while the 6-hydroxylation produced a small excess of the R(+) enantiomer. About 75% of the injected dose of methtryptoline was recovered in the urine as 5- and 6-hydroxylated compounds during the first 24 h period, demonstrating that hydroxylation represents the major metabolic pathway. Treatment with 6-hydroxymethtryptoline-9-carboxylic acid led to a fivefold increase in the urinary excretion of 5-hydroxymethtryptoline during the first 24 h period with a predominance of the S(–)-enantiomer, indicating a much smaller conversion rate than from methtryptoline. It was concluded that hydroxylation of methtryptoline is a likely pathway for the natural formation of 5-hydroxymethtryptoline. 相似文献
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Glen P. Martin Matthew Sperrin Kym I. E. Snell Iain Buchan Richard D. Riley 《Statistics in medicine》2021,40(2):498-517
Clinical prediction models (CPMs) can predict clinically relevant outcomes or events. Typically, prognostic CPMs are derived to predict the risk of a single future outcome. However, there are many medical applications where two or more outcomes are of interest, meaning this should be more widely reflected in CPMs so they can accurately estimate the joint risk of multiple outcomes simultaneously. A potentially naïve approach to multi‐outcome risk prediction is to derive a CPM for each outcome separately, then multiply the predicted risks. This approach is only valid if the outcomes are conditionally independent given the covariates, and it fails to exploit the potential relationships between the outcomes. This paper outlines several approaches that could be used to develop CPMs for multiple binary outcomes. We consider four methods, ranging in complexity and conditional independence assumptions: namely, probabilistic classifier chain, multinomial logistic regression, multivariate logistic regression, and a Bayesian probit model. These are compared with methods that rely on conditional independence: separate univariate CPMs and stacked regression. Employing a simulation study and real‐world example, we illustrate that CPMs for joint risk prediction of multiple outcomes should only be derived using methods that model the residual correlation between outcomes. In such a situation, our results suggest that probabilistic classification chains, multinomial logistic regression or the Bayesian probit model are all appropriate choices. We call into question the development of CPMs for each outcome in isolation when multiple correlated or structurally related outcomes are of interest and recommend more multivariate approaches to risk prediction. 相似文献
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Jackson CC Holter S Pollett A Clendenning M Chou S Senter L Ramphal R Gallinger S Boycott K 《Pediatric blood & cancer》2008,50(6):1268-1270
A 14-year-old male presented with a T4 sigmoid adenocarcinoma, <10 colonic adenomas and multiple café-au-lait macules. Family history was not suggestive of a dominant hereditary form of colorectal cancer. Evaluation of the tumor revealed abnormal immunohistochemical staining of the PMS2 protein and high frequency microsatellite instability. Germline analysis identified biallelic PMS2 missense mutations. A new cancer syndrome caused by biallelic mutations in the mismatch repair genes, including PMS2, is now emerging and is characterized by café-au-lait macules, colonic polyps and a distinctive tumor spectrum. 相似文献
8.
Kevin A. Murray Carolyn J. Hu Hope Pan Jiahui Lu Romany Abskharon Jeannette T. Bowler Gregory M. Rosenberg Christopher K. Williams Gazmend Elezi Melinda Balbirnie Kym F. Faull Harry V. Vinters Paul M. Seidler David S. Eisenberg 《Proceedings of the National Academy of Sciences of the United States of America》2023,120(7)
The amyloid aggregation of alpha-synuclein within the brain is associated with the pathogenesis of Parkinson’s disease (PD) and other related synucleinopathies, including multiple system atrophy (MSA). Alpha-synuclein aggregates are a major therapeutic target for treatment of these diseases. We identify two small molecules capable of disassembling preformed alpha-synuclein fibrils. The compounds, termed CNS-11 and CNS-11g, disaggregate recombinant alpha-synuclein fibrils in vitro, prevent the intracellular seeded aggregation of alpha-synuclein fibrils, and mitigate alpha-synuclein fibril cytotoxicity in neuronal cells. Furthermore, we demonstrate that both compounds disassemble fibrils extracted from MSA patient brains and prevent their intracellular seeding. They also reduce in vivo alpha-synuclein aggregates in C. elegans. Both compounds also penetrate brain tissue in mice. A molecular dynamics–based computational model suggests the compounds may exert their disaggregating effects on the N terminus of the fibril core. These compounds appear to be promising therapeutic leads for targeting alpha-synuclein for the treatment of synucleinopathies.Parkinson’s disease (PD), multiple system atrophy (MSA), and dementia with Lewy bodies (DLB) are neurodegenerative disorders characterized by abnormal accumulation of the protein alpha-synuclein (1). Known as synucleinopathies, these diseases are hallmarked by the fibrillar aggregation of alpha-synuclein in either neurons or glial cells (2). Alpha-synuclein aggregation is potentially causative of disease progression as variants in alpha-synuclein that promote aggregation are associated with early-age disease onset and familial forms of PD and DLB (3). In PD, alpha-synuclein aggregation occurs primarily in dopaminergic neurons, while in MSA, aggregation is primarily in oligodendrocytes (4, 5). Natively, alpha-synuclein functions as a vesicle transport protein and more recently found to be involved in P-body and mRNA stability (6, 7). Alpha-synuclein is an intrinsically disordered protein, which has made the determination of an atomic structure of its soluble form challenging. It has been shown that soluble alpha-synuclein adopts a helical form when bound to cell membranes, while its aggregated form adopts the cross-beta structure typical of other amyloid fibrils (8–10). Multiple structures of fibrillar alpha-synuclein have been determined both of recombinant (11–16) and brain-derived fibrils (17, 18).In addition to primary aggregation, one mechanism by which alpha-synuclein pathology spreads throughout the brain is the prion-like seeding of alpha-synuclein aggregates (19). Alpha-synuclein fibrils can seed the aggregation of soluble native protein, and Lewy body pathology is observed to spread through connected brain regions (19). Aggregation of alpha-synuclein, both primary and seeded, has become a main therapeutic target for synucleinopathies. Antibodies that sequester alpha-synuclein aggregates are currently under development, as well as small molecules that bind monomer and prevent primary aggregation (20). We recently identified several rationally designed peptides and small proteins capable of binding to the growing ends of alpha-synuclein fibrils and preventing fibril elongation and seeding (21, 22). In this current study, we present small molecules capable of disaggregating preformed alpha-synuclein fibrils. We demonstrate the efficacy of these molecules with in vitro studies, cell culture models, and in vivo models using both recombinant and patient brain-derived alpha-synuclein fibrils. We also present a structure-based model to describe their possible mechanism of fibril disaggregation. 相似文献
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