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11.
Frints SG Jun L Fryns JP Devriendt K Teulingkx R Van den Berghe L De Vos B Borghgraef M Chelly J Des Portes V Van Bokhoven H Hamel B Ropers HH Kalscheuer V Raynaud M Moraine C Marynen P Froyen G 《American journal of medical genetics. Part A》2003,(3):367-374
We describe a 59-year-old male (patient A059) with moderate to severe mental retardation (MR) and a pericentric inversion of the X-chromosome: inv(X)(p21.1;q22.1). He had short stature, pectus excavatum, general muscle wasting, and facial dysmorphism. Until now, no other patients with similar clinical features have been described in the literature. Molecular analysis of both breakpoints led to the identification of a novel "Nuclear RNA export factor" (NXF) gene cluster on Xq22.1. Within this cluster, the NXF5 gene was interrupted with subsequent loss of gene expression. Hence, mutation analysis of the NXF5 and its neighboring homologue, the NXF2 gene was performed in 45 men with various forms of syndromic X-linked MR (XLMR) and in 70 patients with nonspecific XLMR. In the NXF5 gene four nucleotide changes: one intronic, two silent, and one missense (K23E), were identified. In the NXF2 gene two changes (one intronic and one silent) were found. Although none of these changes were causative mutations, we propose that NXF5 is a good candidate gene for this syndromic form of XLMR, given the suspected role of NXF proteins is within mRNA export/transport in neurons. Therefore, mutation screening of the NXF gene family in phenotypically identical patients is recommended. 相似文献
12.
Risk correlates of prevalent HIV,hepatitis B virus,and hepatitis C virus infections among noninjecting heroin users 总被引:2,自引:0,他引:2
Gyarmathy VA Neaigus A Miller M Friedman SR Des Jarlais DC 《Journal of acquired immune deficiency syndromes (1999)》2002,30(4):448-456
OBJECTIVE: To examine lifetime correlates of HIV and hepatitis B and C (HBV and HCV) infections among noninjecting heroin users (NIUs). METHODS: Between March 1996 and March 2001, 483 eligible NIUs were tested for HIV, HBV, and HCV antibodies and administered structured interviews. Multivariate logistic regression analyses were stratified by injecting history. RESULTS: Among never-injectors (69.8%), significant (p <.05) correlates were unprotected sex with men who have sex with men (HIV and HBV), unprotected sex with NIUs (HIV), self-reported syphilis infection (HBV), longer duration of heroin use (HBV and HCV), shorter duration of cocaine use (HIV), blood transfusion before 1986 (HIV), and having been tattooed (HCV). Among former injectors (30.2%), significant correlates were receptive syringe sharing (HIV and HBV), frequent lifetime injection (HCV), longer duration of sexual activity (HBV), and having been tattooed (HCV). CONCLUSION: Never-injectors infected with HIV and HBV appear to have become infected mainly through sexual transmission, whereas former injectors appear to have become infected with HIV and HCV mainly though injecting risk and with HBV through both injecting and sexual risk. Interventions targeted at NIUs should prevent unsafe sex as well as the initiation or resumption of injecting. In addition, unhygienic tattooing, which may lead to HCV exposure, should be a focus of prevention efforts. 相似文献
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Semaan S Des Jarlais DC Sogolow E Johnson WD Hedges LV Ramirez G Flores SA Norman L Sweat MD Needle R 《Journal of acquired immune deficiency syndromes (1999)》2002,30(Z1):S73-S93
We examined the effectiveness of 33 U.S.-based HIV intervention studies in reducing the sexual risk behaviors of drug users by reducing unprotected sex or increasing the use of male condoms. The studies, identified as of June 1998, through the HIV/AIDS Prevention Research Synthesis project, were published in 1988 or later, measured behavioral or biologic outcomes, used experimental designs or certain quasi-experimental designs, and reported sufficient data for calculating an effect size for sexual risk reduction. Of the 33 studies, 94% recruited injection drug users; 21% recruited crack users. The mean age of participants was 36 years. Almost all studies were randomized (94%), provided another HIV intervention to the comparison groups (91%), and evaluated behavioral interventions (91%). On average, interventions were conducted in 5 sessions (total, 10 hours) during 4.5 months. Interventions compared with no interventions were strong and significant (k = 3; odds ratio [OR], 0.60; 95% confidence interval [CI], 0.43-0.85). Interventions compared with other HIV interventions showed a modest additional benefit (k = 30; OR, 0.91; 95% CI, 0.81-1.03). When we extrapolated our result (an OR of 0.60) to a population with a 72% prevalence of risk behavior, the proportion of drug users who reduced their risk behaviors was 12.6% greater in the intervention groups than in the comparison groups. Our meta-analysis shows that interventions can lead to sexual risk reduction among drug users and justifies providing interventions to drug users. Developing interventions with stronger effects to further reduce sexual risk behaviors among drug users must remain a high priority. 相似文献
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Friedman SR Kottiri BJ Neaigus A Curtis R Vermund SH Des Jarlais DC 《American journal of epidemiology》2000,152(10):913-922
In many cities, human immunodeficiency virus (HIV)-1 seroprevalence among drug injectors stabilizes at 30-70% for many years without secondary outbreaks that increase seroprevalence by 15% or more. The authors considered how HIV-1 incidence can remain moderate at seroprevalence levels that would give maximum incidence. Previously suggested answers include behavioral risk reduction and network saturation within high-risk subgroups. Among 767 drug injectors studied in 1991-1993, during a period of stable high seroprevalence in New York City, risk behaviors remained common, and networks were far from saturated. The authors suggest a different network-based mechanism: in stable high-prevalence situations, the relatively small sizes of subnetworks of linked seronegatives (within larger networks containing both infected and uninfected persons) may limit infectious outbreaks. Any primary infection outbreak would probably be limited to members of connected subcomponents of seronegatives, and the largest such subcomponent in the study contained only 18 members (of 415 seronegatives). Research and mathematical modeling should study conditions that may affect the size and stability of subcomponents of seronegatives. Finally, if the existence of small, connected components of seronegatives prevents secondary outbreaks, this protection may weaken, and vulnerability to new outbreaks increase, if HIV-1 seroprevalence falls. Thus, in situations of declining prevalence, prevention programs should be maintained or strengthened. 相似文献
17.
Goldie Y.L. Lui Zaklina Kovacevic Vera Richardson Angelica M. Merlot Danuta S. Kalinowski Des R. Richardson 《Oncotarget》2015,6(22):18748-18779
Newer and more potent therapies are urgently needed to effectively treat advanced cancers that have developed resistance and metastasized. One such strategy is to target cancer cell iron metabolism, which is altered compared to normal cells and may facilitate their rapid proliferation. This is supported by studies reporting the anti-neoplastic activities of the clinically available iron chelators, desferrioxamine and deferasirox. More recently, ligands of the di-2-pyridylketone thiosemicarbazone (DpT) class have demonstrated potent and selective anti-proliferative activity across multiple cancer-types in vivo, fueling studies aimed at dissecting their molecular mechanisms of action. In the past five years alone, significant advances have been made in understanding how chelators not only modulate cellular iron metabolism, but also multiple signaling pathways implicated in tumor progression and metastasis. Herein, we discuss recent research on the targeting of iron in cancer cells, with a focus on the novel and potent DpT ligands. Several key studies have revealed that iron chelation can target the AKT, ERK, JNK, p38, STAT3, TGF-β, Wnt and autophagic pathways to subsequently inhibit cellular proliferation, the epithelial-mesenchymal transition (EMT) and metastasis. These developments emphasize that these novel therapies could be utilized clinically to effectively target cancer. 相似文献
18.
Marie Claire Van Hout Des Crowley Siobhan O’Dea Susan Clarke 《Culture, health & sexuality》2019,21(9):1074-1086
Club drug use among gay, bisexual and other men who have sex with men is increasingly normalised within sexual contexts and is associated with increased sexual risk behaviours. The term Chemsex is used to describe sexualised drug use lasting several hours or days with multiple sexual partners. A small pilot study, underpinned by interpretative phenomenological analysis (IPA), was conducted in Dublin, Ireland. Interviews were conducted with 10 men who were experiencing physical and emotional health problems as a consequence of their participation in sexualised drug use and wished to exit the Chemsex scene. Interviews explored experiences of sexualised drug use, motives to partake, the organisation of Chemsex parties and group connectivity, drugs used, harm reduction, pleasure and consequences of participation over time. Four basic themes emerged from the analysis: social and cyber arrangements within the Dublin Chemsex scene; poly drug use and experiences of drug dependence; drug and sexual harm reduction within the Chemsex circle of novices and experts; and sexualised drug use, escapism and compulsive participation. Two higher-order themes were also apparent: first, the reinforcing aspects of drug and sexual pleasure; and second, the interplay between excess drug consumption and sex, and drug dependence. 相似文献
19.
Anneli Uusküla Kristiina Rajaleid Ave Talu Katri Abel-Ollo Don C. Des Jarlais 《The International journal on drug policy》2013,24(4):312-318
AimsHere we report a study aimed at estimating trends in the prevalence of injection drug use between 2005 and 2009 in Estonia.BackgroundDescriptions of behavioural epidemics have received little attention compared with infectious disease epidemics in Eastern Europe.MethodsThe number of injection drug users (IDUs) aged 15–44 each year between 2005 and 2009 was estimated using capture–recapture methodology based on 4 data sources (2 treatment data bases: drug use and non-fatal overdose treatment; criminal justice (drug related offences) and mortality (injection drug use related deaths) data). Poisson log-linear regression models were applied to the matched data, with interactions between data sources ?tted to replicate the dependencies between the data sources. Linear regression was used to estimate average change over time.ResultsThere were 24305, 12,292, 238, 545 records and 8100, 1655, 155, 545 individual IDUs identi?ed in the four capture sources (police, drug treatment, overdose, and death registry, accordingly) over the period 2005–2009. The estimated prevalence of IDUs among the population aged 15–44 declined from 2.7% (1.8–7.9%) in 2005 to 2.0% (1.4–5.0%) in 2008, and 0.9% (0.7–1.7%) in 2009. Regression analysis indicated an average reduction of about 1600 injectors per year.ConclusionWhile the capture–recapture method has known limitations, the results are consistent with other data from Estonia. Identifying the drivers of change in the prevalence of injection drug use warrants further research. 相似文献
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