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The role of COX-2 in angiogenesis and rheumatoid arthritis 总被引:4,自引:0,他引:4
Woods JM Mogollon A Amin MA Martinez RJ Koch AE 《Experimental and molecular pathology》2003,74(3):282-290
Recent evidence suggests that cyclooxygenase (COX)-2 is a mediator of angiogenesis, and COX-2 activity is known to be upregulated in the rheumatoid arthritis (RA) synovium. We examined whether mediation of angiogenesis by COX-2 was occuring in cells of the RA synovium and in microvascular endothelial cells (ECs) that are similar to those found in the RA synovium. We demonstrate that rofecoxib, a selective COX-2 inhibitor, acts directly on human dermal microvascular ECs (HMVECs) to inhibit their chemotactic and tube forming ability. Likewise, pretreatment of HMVECs with rofecoxib significantly inhibited their ability to form tubes induced by conditioned media (CM) of activated RA synovial fibroblasts. When RA synovial fibroblasts were pretreated with rofecoxib for 16 h and then stimulated with interleukin (IL)-1beta, their CM induced significantly less HMVEC tube formation when compared with CM from vehicle-treated RA synovial fibroblasts. ELISAs performed on activated RA fibroblast CM for known proangiogenic factors demonstrated a significant reduction in bFGF, in addition to the expected decrease in PGE(2). Our studies suggest that COX-2-induced angiogenic activity is an active mechanism within diseased synovium and may provide an additional rationale for the use of COX-2 inhibitors in RA. 相似文献
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The reaction of the potassium salt of acrylic acid with the potassium salt of a dicarboxylic acid and 1,4-dibromobutane was applied to the synthesis of three series of acrylate-terminated copolyesters: poly(tetramethylene maleate-co-tetramethylene phthalate) (BMPA), poly(tetramethylene fumarate-co-tetramethylenephthalate) (BFPA) and poly(tetramethylene phthalate-co-tetramethylene succinate) (BPSA). The monofunctional monomer, the potassium salt of acrylic acid, was used for the introduction of double bonds at the end of the chains and for the regulation of the molecular weight of the polyesters. The telechelic copolyesters were characterized by 1H and 13C NMR spectroscopy, in almost all cases providing an acrylate functionality of two. 相似文献
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Shylaja Srinivasan Ling Chen Jennifer Todd Jasmin Divers Samuel Gidding Steven Chernausek Rose A. Gubitosi-Klug Megan M. Kelsey Rachana Shah Mary Helen Black Lynne E. Wagenknecht Alisa Manning Jason Flannick Giuseppina Imperatore Josep M. Mercader Dana Dabelea Jose C. Florez 《Diabetes》2021,70(4):996
The prevalence of type 2 diabetes in youth has increased substantially, yet the genetic underpinnings remain largely unexplored. To identify genetic variants predisposing to youth-onset type 2 diabetes, we formed ProDiGY, a multiethnic collaboration of three studies (TODAY, SEARCH, and T2D-GENES) with 3,006 youth case subjects with type 2 diabetes (mean age 15.1 ± 2.9 years) and 6,061 diabetes-free adult control subjects (mean age 54.2 ± 12.4 years). After stratifying by principal component–clustered ethnicity, we performed association analyses on ∼10 million imputed variants using a generalized linear mixed model incorporating a genetic relationship matrix to account for population structure and adjusting for sex. We identified seven genome-wide significant loci, including the novel locus rs10992863 in PHF2 (P = 3.2 × 10−8; odds ratio [OR] = 1.23). Known loci identified in our analysis include rs7903146 in TCF7L2 (P = 8.0 × 10−20; OR 1.58), rs72982988 near MC4R (P = 4.4 × 10−14; OR 1.53), rs200893788 in CDC123 (P = 1.1 × 10−12; OR 1.32), rs2237892 in KCNQ1 (P = 4.8 × 10−11; OR 1.59), rs937589119 in IGF2BP2 (P = 3.1 × 10−9; OR 1.34), and rs113748381 in SLC16A11 (P = 4.1 × 10−8; OR 1.04). Secondary analysis with 856 diabetes-free youth control subjects uncovered an additional locus in CPEB2 (P = 3.2 × 10−8; OR 2.1) and consistent direction of effect for diabetes risk. In conclusion, we identified both known and novel loci in the first genome-wide association study of youth-onset type 2 diabetes. 相似文献
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Second cancers after medulloblastoma: population-based results from the United States and Sweden 总被引:5,自引:0,他引:5
Alisa M. Goldstein Jonathan Yuen Margaret A. Tucker 《Cancer causes & control : CCC》1997,8(6):865-871
Medulloblastoma, one of the most common central nervous system(CNS)tumors in children, requires aggressive multimodality therapy
including surgery, radiation therapy, and occasionally chemotherapy. Given its intensive treatment regimen and improved survival
during the past 20 years, it is likely that a cohort of survivors will result who may incur consequences of therapy, including
a second cancer. We used population-based data from the United States and Sweden to estimate risks of second neo plasms in
patients with histologically confirmed medulloblastoma (n = 1,262).Overall, there was a 5.4-fold excess of second neoplasms
(95 percent confidence interval = 3.3-8.4) based on 20 observed and 3.7 expected cancers. The second cancers occurred eight
to 432 months after initial diagnosis(median, 73 months) with significantly elevated ratios for all intervals examined except
for less than one year after initial diagnosis. Significantly elevated risks were seen for cancers of the salivary glands,
cervix uteri, brain and CNS, thyroid gland, and acute lymphoblastic leukemia. Of the 15second cancers with treatment data,
seven occurred in the radiation field or within areas of scatter while two others may have been radiation-related. Although
based on small numbers of second cancers, the results suggest that as survival increases, some patients with medulloblastoma
will have an increased risk of a second cancer, particularly a radiation-related cancer. Thus, as survival improves, late-occurring
consequences of diagnosis and treatment will need to be carefully assessed. Identification of patients hypersensitive to radiation
therapy, such as those with Gorlin Syndrome, should also be attempted in order to reduce the sequelae from intensive radiation
exposure.
This revised version was published online in July 2006 with corrections to the Cover Date. 相似文献
8.
Alisa A. Padon Rajiv N. Rimal William DeJong Michael Siegel David Jernigan 《Health communication》2018,33(2):164-173
Underage drinking is a serious public health problem in the United States, and youth exposure to alcohol advertising has been indicated as a possible contributing factor. Although a number of studies have identified advertising content features that youth find appealing, a key limitation of this research is the absence of a broader tool to examine those features, especially those used by alcohol brands that are popular with underage drinkers. We created an index of content elements found in the research literature to be appealing to youth, and then used this index in a content analysis to identify the degree to which youth-appealing content appeared in a sample of alcohol ads that aired on television shows popular among youth. Finally, using bivariate analysis, we tested the relationship between alcohol brands’ use of this content and the popularity of those brands among youth. We found that many of the ads featured youth-appealing content, and that the ads for the alcohol brands most popular among youth had more youth-appealing content than the less popular brands. 相似文献
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ABSTRACT: BACKGROUND: In childhood, attention deficit/hyperactivity disorder (ADHD) is characterized by age-inappropriate levels of inattentiveness/disorganization, hyperactivity/impulsiveness, or a combination thereof. Although the criteria for ADHD are well defined, the long-term consequences in adults and children need to be more comprehensively understood and quantified. We conducted a systematic review evaluating the long-term outcomes (defined as 2 years or more) of ADHD with the goal of identifying long-term outcomes and the impact that any treatment (pharmacological, non-pharmacological, or multimodal) has on ADHD long-term outcomes. METHODS: Studies were identified using predefined search criteria and 12 databases. Studies included were peer-reviewed, primary studies of ADHD longterm outcomes published between January 1980 to December 2010. Inclusion was agreed on by two independent researchers on review of abstracts or full text. Published statistical comparison of outcome results were summarized as poorer than, similar to, or improved versus comparators, and quantified as percentage comparisons of these categories. RESULTS: Outcomes from 351 studies were grouped into 9 major categories: academic, antisocial behavior, driving, non-medicinal drug use/addictive behavior, obesity, occupation, services use, self-esteem, and social function outcomes. The following broad trends emerged: (1) without treatment, people with ADHD had poorer long-term outcomes in all categories compared with people without ADHD, and (2) treatment for ADHD improved long-term outcomes compared with untreated ADHD, although not usually to normal levels. Only English-language papers were searched and databases may have omitted relevant studies. CONCLUSIONS: This systematic review provides a synthesis of studies of ADHD long-term outcomes. Current treatments may reduce the negative impact that untreated ADHD has on life functioning, but does not usually 'normalize' the recipients. 相似文献