全文获取类型
收费全文 | 467篇 |
免费 | 24篇 |
国内免费 | 1篇 |
专业分类
耳鼻咽喉 | 2篇 |
儿科学 | 4篇 |
妇产科学 | 10篇 |
基础医学 | 77篇 |
口腔科学 | 10篇 |
临床医学 | 42篇 |
内科学 | 103篇 |
皮肤病学 | 8篇 |
神经病学 | 28篇 |
特种医学 | 9篇 |
外科学 | 64篇 |
综合类 | 3篇 |
一般理论 | 2篇 |
预防医学 | 43篇 |
眼科学 | 6篇 |
药学 | 32篇 |
中国医学 | 3篇 |
肿瘤学 | 46篇 |
出版年
2023年 | 1篇 |
2022年 | 12篇 |
2021年 | 16篇 |
2020年 | 6篇 |
2019年 | 8篇 |
2018年 | 14篇 |
2017年 | 12篇 |
2016年 | 15篇 |
2015年 | 10篇 |
2014年 | 13篇 |
2013年 | 21篇 |
2012年 | 37篇 |
2011年 | 43篇 |
2010年 | 13篇 |
2009年 | 14篇 |
2008年 | 33篇 |
2007年 | 41篇 |
2006年 | 31篇 |
2005年 | 24篇 |
2004年 | 22篇 |
2003年 | 34篇 |
2002年 | 18篇 |
2001年 | 4篇 |
2000年 | 2篇 |
1999年 | 1篇 |
1998年 | 4篇 |
1997年 | 3篇 |
1996年 | 3篇 |
1995年 | 5篇 |
1994年 | 5篇 |
1993年 | 3篇 |
1992年 | 2篇 |
1991年 | 2篇 |
1990年 | 3篇 |
1989年 | 1篇 |
1988年 | 3篇 |
1987年 | 2篇 |
1986年 | 3篇 |
1984年 | 2篇 |
1982年 | 2篇 |
1980年 | 1篇 |
1978年 | 1篇 |
1977年 | 1篇 |
1975年 | 1篇 |
排序方式: 共有492条查询结果,搜索用时 15 毫秒
1.
Quigley CA Tan JA He B Zhou ZX Mebarki F Morel Y Forest MG Chatelain P Ritzén EM French FS Wilson EM 《Mechanisms of ageing and development》2004,125(10-11):683-695
Partial androgen insensitivity with sex phenotype variation in two unrelated families was associated with missense mutations in the androgen receptor (AR) gene that disrupted the AR NH(2)-terminal/carboxy terminal interaction. Each mutation caused a single amino acid change within the region of the ligand-binding domain that forms activation function 2 (AF2). In one family, the mutation I737T was in alpha helix 4 and in the other F725L was between helices 3 and 4. Neither mutation altered androgen binding as determined by assays of mutant AR in the patient's cultured genital skin fibroblasts or of recombinant mutant receptors transfected into COS cells. In transient cotransfection assays in CV1 cells, transactivation with the AR mutants at low concentrations of DHT was reduced several fold compared with wild-type AR but increased at higher concentrations. Defects in NH(2)-terminal/carboxy terminal interactions were identified in mammalian two hybrid assays. In similar assays, there was reduced binding of the p160 coactivators TIF2/SRC2 and SRC1 to the mutant AR ligand binding domains (LBD). In the family with AR I737T, sex phenotype varied from severely defective masculinization in the proband to a maternal great uncle whose only manifestation of AIS was severe gynecomastia. He was fertile and passed the mutation to two daughters. The proband of the F725L family was also incompletely masculinized but was raised as a male while his half-sibling by a different father was affected more severely and reared as a female. These studies indicate that the function of an AR AF2 mutant in male development can vary greatly depending on the genetic background. 相似文献
2.
Christine T. Kovner Maja Djukic Jin Jun Jason Fletcher Farida K. Fatehi Carol S. Brewer 《Nursing outlook》2018,66(2):160-167
Background
The Institute of Medicine (IOM) report, The Future of Nursing, included recommendations to increase nurse diversity, the percent of nurses obtaining a bachelor’s degree, and inter-professional education.Purpose
The purpose of this paper is to report the progress toward achievement of these recommendations.Methods
We used a longitudinal, multi-state data from four cohorts of nurses newly licensed in 2004 to 2005, 2007 to 2008, 2010 to 2011, and 2014 to 2015 to examine and compare the trends.Finding
The percentage of males who became licensed increased, from 8.8% in 2004 to 2005 cohort to 13.6% in the 2014 to 2015 cohort. The percentage of white-non-Hispanic nurses who were licensed decreased from 78.9% in 2007 to 2008 to 73.8% in 2014 to 2015. These differences primarily reflect an increase in white-Hispanic nurses. More nurses are obtaining a bachelor’s degree as their first professional degree, from 36.6% in 2004 to 2005 cohort to 48.5% in 2014 to 2015 cohort. About 40% of the 2014 to 2015 cohort reported that they learned to work in inter-professional teams. Collegial nurse-physician relations had an upward positive trajectory over time increasing almost 7%.Discussion
The diversity and education of new nurses have increased, but are short of meeting the IOM recommendations. 相似文献3.
4.
5.
Tumour suppressor gene inactivation is critical to the pathogenesis of cancers; such loss of function may be mediated by irreversible processes such as gene deletion or mutation. Alternatively tumour suppressor genes may be inactivated via epigenetic processes a reversible mechanism that promises to be more amenable to treatment by therapeutic agents. The CpG dinucleotide is under-represented in the genome, but it is found in clusters within the promoters of some genes, and methylation of these CpG islands play a critical role in the control of gene expression. Inhibitors of the DNA methyltransferases DNMT1 and DNMT3b have been used in a clinical setting, these nucleotide analogues lack specificity but the side effects of low dose treatments were minimal and in 2004 Vidaza (5-azacitidine) was licensed for use in myelodysplastic syndrome. Methylation inhibitors are also entering trials in conjunction with another class of epigenetic modifiers, the histone deacetylase inhibitors and this epigenetic double bullet offers hope of improved treatment regimes. Recently there has been a plethora of reports demonstrating epigenetic inactivation of genes that play important roles in development of cancer, including Ras-association domain family of genes. Epigenetic inactivation of RASSF1A (Ras-association domain family 1, isoform A) is one of the most common molecular changes in cancer. Hypermethylation of the RASSF1A promoter CpG island silences expression of the gene in many cancers including lung, breast, prostate, glioma, neuroblastoma and kidney cancer. Several recent studies have illustrated the diagnostic and prognostic potential of RASSF1A methylation. This presents RASSF1A methylation as an attractive biomarker for early cancer detection which, for most cancers, results in improved clinical outcome. DNA methylation analysis is applicable to a range of body fluids including serum, urine, bronchioalveolar lavage and sputum. The ease with which these body fluids can be acquired negates the need for invasive procedures to obtain biopsy material. This review will discuss the feasibility of using RASSF1A methylation as a diagnostic and prognostic marker in cancer management. 相似文献
6.
Taghreed Shams MBBS FRCSC Belal Firwana MD Farida Habib PhD Abeer Alshahrani MBBS Badria AlNouh MBBS Mohammad Hassan Murad MD Mazen Ferwana MD 《Journal of general internal medicine》2014,29(1):204-213
Background
Hot flashes are the most commonly reported vasomotor symptom during the peri- and early post-menopausal period.Objectives
To systematically review, appraise and summarize the evidence of the impact of different SSRIs on peri-menopausal hot flashes in healthy women in randomized, controlled trials.Methods
A comprehensive literature search was conducted of MEDLINE?, EMBASE, the Cochrane Central Register of Controlled Trials, Web of Science and Scopus through March 2013. Two independent reviewers selected studies and extracted data. Random effects meta-analysis was used to pool outcomes across studies, and Bayesian mixed treatment methods were used to rank SSRIs in terms of effectiveness.Results
We included a total of 11 randomized controlled trials with good methodological quality enrolling 2,069 menopausal and post-menopausal women (follow-up 1–9 months, mean age 36–76 years, mean time since menopause 2.3–6.6 years). Compared with placebo, SSRIs were associated with a statistically significant decrease in hot flash frequency (difference in means ?0.93; 95 % CI ?1.46 to ?0.37; I2 = 21 %) and severity assessed by various scales (standardized difference in means ?0.34; 95 % CI ?0.59 to ?0.10; I2 = 47 %). Adverse events did not differ from placebo. Mixed treatment comparison analysis demonstrated the superiority of escitalopram compared to other SSRIs in terms of efficacy.Conclusion
SSRI use is associated with modest improvement in the severity and frequency of hot flashes but can also be associated with the typical profile of SSRI adverse effects. 相似文献7.
Khalil Mehindate Reem Al-Daccak Farida Damdoumi Walid Mourad 《European journal of immunology》1996,26(9):2075-2080
Although staphylococcal enterotoxin A (SEA), B (SEB), and toxic shock syndrome toxin 1 (TSST-1) bind to major histocompatibility complex (MHC) class II molecules, they differ in their mode of binding. Signaling induced by these toxins via MHC class II molecules seems to be largely mediated by their mode of interaction. In the present study, we have demonstrated that contrary to SEA, stimulation of the human monocytic cell line THP-1 with SEB or TSST-1 failed to induce interleukin-1β or tumor necrosis factor-α gene expression. Treatment of THP-1 cells with interferon-γ increased the level of MHC class II expression but did not enhance the SEB and TSST-1 response. However, cross-linking of SEB or TSST-1 bound to MHC class II molecules with specific antibodies leads to cytokine gene expression, indicating that dimerization of class II molecules is a requirement for this superantigen-induced response. The presence of anti-CD40 antibodies in the course of SEB or TSST-1 stimulation overcomes this requirement, indicating that certain signal(s) induced via CD40 molecules can replace those induced by dimerization of class II molecules. Pretreatment with anti-lymphocyte functional antigen-1 (LFA-1) antibodies completely inhibited SEA-induced response as well as that induced by SEB or TSST-1 in the presence of CD40 antibodies, supporting the involvement of LFA-1 intercellular adhesion molecule system in these responses. The entirety of these results demonstrate clearly that dimerization of class II molecules is a prerequisite for superantigen-induced T cell-independent cytokine gene expression which can be replaced by signaling via CD40 in an LFA-1-dependent system. 相似文献
8.
Francisco Torres-Bondia Farida Dakterzada Leonardo Galvn Miquel Buti Gaston Besanson Eric Grill Roman Buil Jordi de Batlle Gerard Piol-Ripoll 《The international journal of neuropsychopharmacology / official scientific journal of the Collegium Internationale Neuropsychopharmacologicum (CINP)》2022,25(4):261
BackgroundBenzodiazepines (BZDs) and Z-drugs (BZDRs) are among the most prescribed medications for anxiety and insomnia, especially among older adults. Our objective was to investigate the association between the use of BZDRs and the risk of dementia.MethodsA community-based retrospective cohort study was conducted based on the data available from 2002 to 2015 in Catalan Health Service. This cohort included all BZDR users (N = 83 138) and nonusers (N = 84 652) older than 45 years. A minimum 5-year lag window and an adjustment for psychiatric problems were applied for the data analysis.ResultsThe hazard ratio (HR) for the risk of incident dementia among BZDR users was 1.22 (95% CI = 1.15 to 1.31). This risk was not significant after adjusting the data confounding factors (HR = 1.01; 95% CI = 0.94 to 1.08). We observed a higher risk with short-to-intermediate half-life BZDs (HR = 1.11; 95% CI = 1.04 to 1.20) and Z-drugs (HR = 1.20; 95% CI = 1.07 to 1.33) than for intermediate-to-long half-life BZDs (HR = 1.01; 95% CI = 0.94 to 1.08). We demonstrated a higher risk of incident dementia (HR = 1.23; 95% CI = 1.07 to 1.41 and odds ratio = 1.38; 95% CI = 1.27 to 1.50, respectively) in patients who received 91 to 180 defined daily doses (DDDs) and >180 DDDs compared with patients who received <90 DDD. Regarding patient sex, the risk of dementia was higher in women than in men.ConclusionWe found that the incidence of dementia was not higher among all BZDR users. Short half-life BZDs and Z-drugs increased the risk of dementia at the highest doses, especially in female patients, showing a dose-response relationship. 相似文献
9.
10.