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101.
Rickman L Fiegler H Shaw-Smith C Nash R Cirigliano V Voglino G Ng BL Scott C Whittaker J Adinolfi M Carter NP Bobrow M 《Journal of medical genetics》2006,43(4):353-361
Background
Karyotype analysis has been the standard method for prenatal cytogenetic diagnosis since the 1970s. Although highly reliable, the major limitation remains the requirement for cell culture, resulting in a delay of as much as 14 days to obtaining test results. Fluorescent in situ hybridisation (FISH) and quantitative fluorescent PCR (QF‐PCR) rapidly detect common chromosomal abnormalities but do not provide a genome wide screen for unexpected imbalances. Array comparative genomic hybridisation (CGH) has the potential to combine the speed of DNA analysis with a large capacity to scan for genomic abnormalities. We have developed a genomic microarray of approximately 600 large insert clones designed to detect aneuploidy, known microdeletion syndromes, and large unbalanced chromosomal rearrangements.Methods
This array was tested alongside an array with an approximate resolution of 1 Mb in a blind study of 30 cultured prenatal and postnatal samples with microscopically confirmed unbalanced rearrangements.Results
At 1 Mb resolution, 22/30 rearrangements were identified, whereas 29/30 aberrations were detected using the custom designed array, owing to the inclusion of specifically chosen clones to give increased resolution at genomic loci clinically implicated in known microdeletion syndromes. Both arrays failed to identify a triploid karyotype. Thirty normal control samples produced no false positive results.Conclusions
Analysis of 30 uncultured prenatal samples showed that array CGH is capable of detecting aneuploidy in DNA isolated from as little as 1 ml of uncultured amniotic fluid; 29/30 samples were correctly diagnosed, the exception being another case of triploidy. These studies demonstrate the potential for array CGH to replace conventional cytogenetics in the great majority of prenatal diagnosis cases. 相似文献102.
Richard A Nash Alessandra Takatu Ziding Feng Sherrill Slichter Kraig Abrams German Espino M John Gass George E Georges Peter A McSweeney Howard M Shulman Rainer Storb 《Biology of blood and marrow transplantation》2002,8(7):360-367
This study investigates the potential role of the recombinant c-mpl ligands (recombinant human thrombopoietin [rhTPO] and pegylated recombinant human megakaryocyte growth and development factor [PEG-rhMGDF]) on the recovery of platelet counts after TBI with and without allogeneic hematopoietic stem cell transplantation (HSCT) in an established canine model. Initially, 3 cohorts, each with 2 nonirradiated dogs, received increasing doses of rhTPO (5 microg/kg per day; 10 microg/kg per day; 20 microg/kg per day) for 7 days to determine the optimal dose. The dose of 10 microg/kg per day of rhTPO was selected for subsequent studies. Ten dogs then received either rhTPO or placebo for 28 days after 200 cGy TBI without HSCT. The rhTPO group had fewer days with platelet counts <20,000/microL (9.8 days versus 17.8 days, P < .05) and significantly increased granulocyte counts (n = 5) compared to the controls (n = 5). RhTPO-specific antibodies developed in 2 dogs, which caused a significant but transient decrease of the platelet counts. Retreatment of these sensitized dogs with rhTPO resulted in profound transient decreases in platelet counts. In the next study, 20 dogs received either PEG-rhMGDF or placebo for 21 days after 920 cGy TBI and allogeneic HSCT. The median time to platelet recovery (>20,000/microL) for the PEG-rhMGDF group (n = 10) was 14.0 days compared to 15.5 days for the control group (n = 10; log rank, P = .35). There were no significant differences in the total time to platelet counts <20,000/microL or in the time to recover neutrophil counts >500/microL. The effects of rhTPO on recovery of platelet and granulocyte counts after sublethal TBI were modest, and no effects of PEG-rhMGDF were observed on hematopoietic recovery after high-dose TBI and allogeneic HSCT. The significant effect that rhTPO-specific antibodies had on the platelet counts may limit the clinical role of recombinant c-mpl ligands unless sensitization can be prevented. 相似文献
103.
Fordyce EJ Singh TP Nash D Gallagher B Forlenza S 《Journal of acquired immune deficiency syndromes (1999)》2002,30(1):111-118
BACKGROUND: Since the advent of combined antiretroviral therapy in 1996, substantial decreases in HIV-related morbidity and mortality have been observed in the United States and other developed countries. To assess the effects on overall survival and for specific AIDS-defining illnesses (ADIs), survival among persons with AIDS (PWAs) in New York City (NYC) before and after the introduction of combination therapy was investigated. METHODS: Survival among 79,878 PWAs diagnosed between 1990 and 1998 and reported through March 2001 was estimated. Cumulative survival at 24 months among PWAs was estimated by actuarial methods, and Cox proportional hazards model adjusted for covariates was used to estimate the relative hazard (RH) of death for specific ADIs over time. RESULTS: Overall cumulative survival at 24 months increased from 43% among PWAs diagnosed during 1990-1995 to 76% for those diagnosed 1996-1998. Improving survival for all ADIs was found among PWAs diagnosed after 1995, but changes for immunoblastic lymphoma, primary lymphoma of the brain, and invasive cervical cancer were only moderate and were statistically (p >.05) insignificant. Burkitt lymphoma, immunoblastic lymphoma, invasive cervical cancer, and primary lymphoma of the brain had the highest RH of death among PWAs diagnosed after 1995. CONCLUSIONS: Substantial improvements in survival after 1995 were found for all PWAs but varied by gender, race, risk, socioeconomic status, and specific ADIs. Consistent with other studies, neoplastic ADIs have shown less improvement than other diseases after 1995. The relatively poor outcome of PWAs with neoplastic diseases requires further investigation. 相似文献
104.
Background
Overweight and obesity prevalence is rapidly rising in developing countries. The reading and understanding of nutrition information on food packages has been shown to improve food choices and instill healthy eating habits in individuals.Objective
The aim of this study was to describe the prevalence of food label usage and understanding among urban and rural adults in Zimbabwe and its association with demographic and socio economic factors.Methods
A cross sectional study was conducted on 320 adults (147 urban and 173 rural) using a validated questionnaire adapted from previous similar studies. Data were analysed using SPSS-17 statistical software.Results
A high proportion (77.2%) of the respondents read food labels. Food label reading differed significantly by educational status (p<0.05), employment status (p<0.05) and locality (p<0.05). Only 40.9% of food label readers mostly understood the information on the food labels. More urban shoppers (86.1%) read food labels than their rural counterparts (66.7%). A significant number of participants (80.6%) indicated they would like to be educated on the meaning of food labels and 80.3% preferred the nutrition information on food labels to be simplified.Conclusion
The study found above average reported reading of nutrition information on food labels with partial understanding. Efforts should be made to determine how all consumers could be made to understand the nutrition information on food labels and use it effectively in decision making. 相似文献105.
In this study the verbal fluency procedure was used to investigate the organization of semantic and phonological representations in children with Down syndrome (DS) and typically developing children, matched pairwise for receptive vocabulary age. Productivity was found to be significantly reduced in the DS group in both the semantic and the phonological tasks. However, group differences in the number of clusters as opposed to cluster size suggest that this may reflect less efficient retrieval strategies rather than differences in the organization of linguistic representations. Together the findings point to executive deficits in Down syndrome rather than deviant language processes. 相似文献
106.
Germline mutations of the CDKN2 gene in UK melanoma families 总被引:4,自引:1,他引:4
Harland M; Meloni R; Gruis N; Pinney E; Brookes S; Spurr NK; Frischauf AM; Bataille V; Peters G; Cuzick J; Selby P; Bishop DT; Bishop JN 《Human molecular genetics》1997,6(12):2061-2067
Germline mutations in CDKN2 on chromosome 9p21, which codes for the cyclin
D kinase inhibitor p16, and more rarely, mutations in the gene coding for
CDK4, the protein to which p16 binds, underlie susceptibility in some
melanoma families. We have sequenced all exons of CDKN2 and analysed the
CDK4 gene for mutations in 27 UK families showing evidence of
predisposition to melanoma. Five different germline mutations in CDKN2 were
found in six families. Three of the mutations (Met53Ile, Arg24Pro and
23ins24) have been reported previously. We have identified two novel CDKN2
mutations (88delG and Ala118Thr) which are likely to be associated with the
development of melanoma, because of their co-segregation with the disease
and their likely functional effect on the CDKN2 protein. In binding assays
the protein expressed from the previously described mutation, Met53Ile, did
not bind to CDK4/CDK6, confirming its role as a causal mutation in the
development of melanoma. Ala118Thr appeared to be functional in this assay.
Arg24Pro appeared to bind to CDK6, but not to CDK4. No mutations were
detected in exon 2 of CDK4, suggesting that causal mutations in this gene
are uncommon. The penetrance of these mutant CDKN2 genes is not yet
established, nor is the risk of non-melanoma cancer to gene carriers.
相似文献
107.
McGettrick HM Hunter K Moss PA Buckley CD Rainger GE Nash GB 《Journal of leukocyte biology》2009,85(1):98-107
The kinetics and regulatory mechanisms of T cell migration through the endothelium have not been fully defined. In experimental, filter-based assays in vitro, transmigration of lymphocytes takes hours, compared with minutes, in vivo. We cultured endothelial cell (EC) monolayers on filters, solid substrates, or collagen gels and treated them with TNF-alpha, IFN-gamma, or both prior to analysis of lymphocyte migration in the presence or absence of flow. PBL, CD4+ cells, or CD8+ cells took many hours to migrate through EC-filter constructs for all cytokine treatments. However, direct microscopic observations of EC filters, which had been mounted in a flow chamber, showed that PBL crossed the endothelial monolayer in minutes and were highly motile in the subendothelial space. Migration through EC was also observed on clear plastic, with or without flow. After a brief settling without flow, PBL and isolated CD3+ or CD4+ cells crossed EC in minutes, but the numbers of migrated cells varied little with time. Close observation revealed that lymphocytes migrated back and forth continuously across endothelium. Under flow, migration kinetics and the proportions migrating back and forth were altered little. On collagen gels, PBL again crossed EC in minutes and migrated back and forth but showed little penetration of the gel over hours. In contrast, neutrophils migrated efficiently through EC and into gels. These observations suggest a novel model for lymphoid migration in which EC support migration but retain lymphocytes (as opposed to neutrophils), and additional signal(s) are required for onward migration. 相似文献
108.
Sensory gating deficits are seen in individuals with schizophrenia and schizotypal disorders, yet smoking influence, regional or lateral difference effects are rarely assessed. We examined sensory gating in smokers and non-smokers within university-level high and low schizotypal personality (HiS and LoS) groups using [Raine, A., 1991. The Schizotypal Personality Questionnaire (SPQ): A measure of schizotypal personality based on DSM-III-R criteria. Schizophr. Bull. 17, 555-564] Schizotypal Personality Questionnaire. Among 39 (18 men; 19 smokers) right-handed undergraduates, a paired-tone paradigm (40 pairs; 10 s ISI; 70 dB, 1000 Hz) was presented in two conditions (smokers while abstaining and after smoking). Sensory gating [S2(P50-N40)/S1(P50-N40)] was assessed at frontal, fronto-central, central, centro-parietal, and parietal midline and lateralized sites. Sensory gating was better at (1) midline than left/right hemispheric sites, and (2) fronto-central and central midline sites. At fronto-central/central lateral sites, (1) among non-smokers, better sensory gating occurred in LoS than HiS, (2) among smokers, better sensory gating occurred in HiS than LoS, and (3) among LoSs, smokers showed less sensory gating than non-smokers. No acute smoking effects emerged. Unlike schizophrenia studies, smoking did not impact sensory gating. Differences among smokers and non-smokers in LoS and HiS groups reinforce need to evaluate both smoking and schizotypal characteristics, as well as midline and lateral sites in anterior to posterior regions, in sensory gating studies. 相似文献
109.
110.
Brett T. Litz Nathan Stein Eileen Delaney Leslie Lebowitz William P. Nash Caroline Silva Shira Maguen 《Clinical psychology review》2009
Throughout history, warriors have been confronted with moral and ethical challenges and modern unconventional and guerilla wars amplify these challenges. Potentially morally injurious events, such as perpetrating, failing to prevent, or bearing witness to acts that transgress deeply held moral beliefs and expectations may be deleterious in the long-term, emotionally, psychologically, behaviorally, spiritually, and socially (what we label as moral injury). Although there has been some research on the consequences of unnecessary acts of violence in war zones, the lasting impact of morally injurious experience in war remains chiefly unaddressed. To stimulate a critical examination of moral injury, we review the available literature, define terms, and offer a working conceptual framework and a set of intervention strategies designed to repair moral injury. 相似文献