全文获取类型
收费全文 | 691篇 |
免费 | 34篇 |
国内免费 | 2篇 |
专业分类
耳鼻咽喉 | 1篇 |
儿科学 | 46篇 |
妇产科学 | 6篇 |
基础医学 | 59篇 |
口腔科学 | 9篇 |
临床医学 | 80篇 |
内科学 | 253篇 |
皮肤病学 | 14篇 |
神经病学 | 6篇 |
特种医学 | 63篇 |
外科学 | 107篇 |
综合类 | 27篇 |
预防医学 | 28篇 |
眼科学 | 2篇 |
药学 | 16篇 |
肿瘤学 | 10篇 |
出版年
2022年 | 3篇 |
2021年 | 5篇 |
2019年 | 7篇 |
2018年 | 15篇 |
2017年 | 12篇 |
2016年 | 12篇 |
2015年 | 6篇 |
2014年 | 13篇 |
2013年 | 23篇 |
2012年 | 18篇 |
2011年 | 29篇 |
2010年 | 28篇 |
2009年 | 31篇 |
2008年 | 37篇 |
2007年 | 38篇 |
2006年 | 50篇 |
2005年 | 33篇 |
2004年 | 36篇 |
2003年 | 28篇 |
2002年 | 29篇 |
2001年 | 18篇 |
2000年 | 18篇 |
1999年 | 12篇 |
1998年 | 21篇 |
1997年 | 28篇 |
1996年 | 15篇 |
1995年 | 15篇 |
1994年 | 10篇 |
1993年 | 12篇 |
1992年 | 8篇 |
1991年 | 5篇 |
1989年 | 10篇 |
1988年 | 7篇 |
1987年 | 6篇 |
1986年 | 6篇 |
1985年 | 20篇 |
1984年 | 9篇 |
1983年 | 5篇 |
1982年 | 6篇 |
1981年 | 7篇 |
1980年 | 5篇 |
1979年 | 2篇 |
1978年 | 3篇 |
1977年 | 2篇 |
1976年 | 5篇 |
1975年 | 3篇 |
1970年 | 2篇 |
1969年 | 2篇 |
1968年 | 3篇 |
1967年 | 2篇 |
排序方式: 共有727条查询结果,搜索用时 187 毫秒
91.
Rafiq S Melzer D Weedon MN Lango H Saxena R Scott LJ;DIAGRAM Consortium Palmer CN Morris AD McCarthy MI Ferrucci L Hattersley AT Zeggini E Frayling TM 《Diabetologia》2008,51(12):2205-2213
Aims/hypothesis There are strong associations between measures of inflammation and type 2 diabetes, but the causal directions of these associations
are not known. We tested the hypothesis that common gene variants known to alter circulating levels of inflammatory proteins,
or known to alter autoimmune-related disease risk, influence type 2 diabetes risk.
Methods We selected 46 variants: (1) eight variants known to alter circulating levels of inflammatory proteins, including those in
the IL18, IL1RN, IL6R, MIF, PAI1 (also known as SERPINE1) and CRP genes; and (2) 38 variants known to predispose to autoimmune diseases, including type 1 diabetes. We tested the associations
of these variants with type 2 diabetes using a meta-analysis of 4,107 cases and 5,187 controls from the Wellcome Trust Case
Control Consortium, the Diabetes Genetics Initiative, and the Finland–United States Investigation of NIDDM studies. We followed
up associated variants (p < 0.01) in a further set of 3,125 cases and 3,596 controls from the UK.
Results We found no evidence that inflammatory or autoimmune disease variants are associated with type 2 diabetes (at p ≤ 0.01). The OR observed between the variant altering IL-18 levels, rs2250417, and type 2 diabetes (OR 1.00 [95% CI 0.99–1.03]),
is much lower than that expected given (1) the effect of the variant on IL-18 levels (0.28 SDs per allele); and (2) estimates,
based on other studies, of the correlation between IL-18 levels and type 2 diabetes risk (approximate OR 1.15 [95% CI 1.09–1.21]
per 0.28 SD increase in IL-18 levels).
Conclusions/interpretation Our study provided no evidence that variants known to alter measures of inflammation, autoimmune or inflammatory disease risk,
including type 1 diabetes, alter type 2 diabetes risk.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorised users. 相似文献
92.
Maggie H. Shepherd Beverley M. Shields Michelle Hudson Ewan R. Pearson Christopher Hyde Sian Ellard Andrew T. Hattersley Kashyap A. Patel for the UNITED study 《Diabetologia》2018,61(12):2520-2527
Aims/hypothesis
Treatment change following a genetic diagnosis of MODY is frequently indicated, but little is known about the factors predicting future treatment success. We therefore conducted the first prospective study to determine the impact of a genetic diagnosis on individuals with GCK-, HNF1A- or HNF4A-MODY in the UK, and to identify clinical characteristics predicting treatment success (i.e. HbA1c ≤58 mmol/mol [≤7.5%]) with the recommended treatment at 2 years.Methods
This was an observational, prospective, non-selective study of individuals referred to the Exeter Molecular Genetic Laboratory for genetic testing from December 2010 to December 2012. Individuals from the UK with GCK- or HNF1A/HNF4A-MODY who were not on recommended treatment at the time of genetic diagnosis, and who were diagnosed below the age of 30 years and were currently aged less than 50 years, were eligible to participate.Results
A total of 44 of 58 individuals (75.9%) changed treatment following their genetic diagnosis. Eight individuals diagnosed with GCK-MODY stopped all diabetes medication without experiencing any change in HbA1c (49.5 mmol/mol [6.6%] both before the genetic diagnosis and at a median of 1.25 years’ follow-up without treatment, p?=?0.88). A total of 36 of 49 individuals (73.5%) diagnosed with HNF1A/HNF4A-MODY changed treatment; however, of the 21 of these individuals who were being managed with diet or sulfonylurea alone at 2 years, only 13 (36.1% of the population that changed treatment) had an HbA1c ≤58 mmol/mol (≤7.5%). These individuals had a shorter diabetes duration (median 4.6 vs 18.1 years), lower HbA1c (58 vs 73 mmol/mol [7.5% vs 8.8%]) and lower BMI (median 24.2 vs 26.0 kg/m2) at the time of genetic diagnosis, compared with individuals (n?=?23/36) with an HbA1c >58 mmol/mol (>7.5%) (or <58 mmol/mol [<7.5%] on additional treatment) at the 2 year follow-up. Overall, 64% (7/11) individuals with a diabetes duration of ≤11 years and an HbA1c of ≤69 mmol/mol (≤8.5%) at time of the genetic test achieved good glycaemic control (HbA1c ≤58 mmol/mol [≤7.5%]) with diet or sulfonylurea alone at 2 years, compared with no participants with a diabetes duration of >11 years and an HbA1c of >69 mmol/mol (>8.5%) at the time of genetic diagnosis.Conclusions/interpretation
In participants with GCK-MODY, treatment cessation was universally successful, with no change in HbA1c at follow-up. In those with HNF1A/HNF4A-MODY, a shorter diabetes duration, lower HbA1c and lower BMI at genetic diagnosis predicted successful treatment with sulfonylurea/diet alone, supporting the need for early genetic diagnosis and treatment change. Our study suggests that, in individuals with HNF1A/HNF4A-MODY with a longer duration of diabetes (>11 years) at time of genetic test, rather than ceasing current treatment, a sulfonylurea should be added to existing therapy, particularly in those who are overweight or obese and have a high HbA1c.93.
94.
Davies M Lavalle-González F Storms F Gomis R;AT.LANTUS Study Group 《Diabetes, obesity & metabolism》2008,10(5):387-399
Objective: For many patients with type 2 diabetes, oral antidiabetic agents (OADs) do not provide optimal glycaemic control, necessitating insulin therapy. Fear of hypoglycaemia is a major barrier to initiating insulin therapy. The AT.LANTUS study investigated optimal methods to initiate and maintain insulin glargine (LANTUS®, glargine, Sanofi-aventis, Paris, France) therapy using two treatment algorithms. This subgroup analysis investigated the initiation of once-daily glargine therapy in patients suboptimally controlled on multiple OADs. Research Design and Methods: This study was a 24-week, multinational (59 countries), multicenter (611), randomized study. Algorithm 1 was a clinic-driven titration and algorithm 2 was a patient-driven titration. Titration was based on target fasting blood glucose ≤100 mg/dl (≤5.5 mmol/l). Algorithms were compared for incidence of severe hypoglycaemia [requiring assistance and blood glucose <50 mg/dl (<2.8 mmol/l)] and baseline to end-point change in haemoglobin A1c (HbA1c). Results: Of the 4961 patients enrolled in the study, 865 were included in this subgroup analysis: 340 received glargine plus 1 OAD and 525 received glargine plus >1 OAD. Incidence of severe hypoglycaemia was <1%. HbA1c decreased significantly between baseline and end-point for patients receiving glargine plus 1 OAD (−1.4%, p < 0.001; algorithm 1 −1.3% vs. algorithm 2 −1.5%; p = 0.03) and glargine plus >1 OAD (−1.7%, p < 0.001; algorithm 1 −1.5% vs. algorithm 2 −1.8%; p = 0.001). Conclusions: This study shows that initiation of once-daily glargine with OADs results in significant reduction of HbA1c with a low risk of hypoglycaemia. The greater reduction in HbA1c was seen in patients randomized to the patient-driven algorithm (algorithm 2) on 1 or >1 OAD. 相似文献
95.
96.
Eosinophil functions can be modulated by several cytokines such as granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin- 3 (IL-3), and IL-5. We have investigated the modulatory role of these cytokines on the interaction of human eosinophils with opsonized particles (serum-treated zymosan [STZ]). Addition of STZ to eosinophils isolated from the peripheral blood of normal human donors resulted in an interaction of the STZ particles with only 15% to 25% of the cells. Treatment of the eosinophils with GM-CSF, IL-3, or IL-5 strongly enhanced both the rate of particle binding and the percentage of eosinophils binding STZ. The effect of the cytokines is most likely mediated by a change in affinity of the complement receptor type 3 (CR3) on the eosinophils for the complement fragment iC3b on the STZ particles. This is indicated by the observation that (1) the effect of the cytokines on STZ binding was prevented by a monoclonal antibody against the iC3b-binding site on CR3 and (2) the enhanced binding was already apparent before upregulation of CR3 on the cell surface was observed. In a previous study, similar results were obtained with platelet-activating factor (PAF)-primed eosinophils. Because we found that the cytokines strongly enhanced the STZ-induced PAF synthesis, we investigated the role of both released PAF and cell-associated PAF in the priming phenomenon by the cytokines. Cytokine priming appeared to be largely independent of the synthesis of PAF. 相似文献
97.
Deprivation of dietary nucleotides decreases protein synthesis in the liver and small intestine in rats 总被引:1,自引:0,他引:1
AT Lopez-Navarro MA Ortega J Peragon JD Bueno A Gil A Sanchez-Pozo 《Gastroenterology》1996,110(6):1760-1769
BACKGROUND & AIMS: Dietary nucleotides are reported to influence the growth and functioning of the liver and small intestine. The aim of this study was to examine the mechanism by which nucleotides exert their effects in these tissues by assessing protein synthesis activity and related parameters in the presence or absence of dietary nucleotides. METHODS: Rats were fed a purified diet with or without nucleotides for 10 days. Fractional protein synthesis rate, RNA and DNA concentrations, polysome size distribution, and number of ribosomes were assessed. RESULTS: Fractional protein synthesis rates of the liver and small intestine were lower in the nucleotide-deprived group than in the control group. In the liver, RNA concentration was also lower in the nucleotide-deprived group, but values in the small intestine were similar in the two groups. In the liver, deprivation of nucleotides resulted in a reduction in the number of ribosomes and in polysome breakdown. Protein and DNA concentrations did not vary in the liver; however, the concentration of DNA was lower in the small intestine of the nucleotide-deprived group than in the control group. CONCLUSIONS: Dietary nucleotides can modulate protein synthesis in the liver and small intestine as a result of tissue-specific nucleic acid changes. (Gastroenterology 1996 Jun;110(6):1760-9) 相似文献
98.
99.
100.
J. T. E. Cook D. C. Shields R. C. L. Page J. C. Levy A. T. Hattersley J. A. G. Shaw H. A. W. Neil J. S. Wainscoat Dr. R. C. Turner 《Diabetologia》1994,37(12):1231-1240
Summary Non-insulin-dependent diabetes mellitus (NIDDM) has a substantial genetic component, but the mode of inheritance and the molecular basis are unknown. We have undertaken segregation analysis of NIDDM after studying 247 subjects in 59 Caucasian nuclear pedigrees ascertained without regard to family history of the disorder. The analyses were performed using POINTER and COMDS, which are computer programs which apply statistical models to the data. POINTER analysis was performed defining the phenotype as a presence or absence of hyperglycaemia. Among single locus hypotheses, the analyses rejected a recessive model and favoured a dominant model, but could not statistically show that this fitted better than a mixed model (a single locus against a polygenic background) or a polygenic model. COMDS analysis assumed a continuum of hyperglycaemia from normality to NIDDM, classified family members into a series of diathesis classes with increasing plasma glucose levels and compared the distribution with that found by screening the normal population. This analysis improved the likelihood of a dominant single locus model and suggested a gene frequency of 7.4%. It raised the possibility of a second locus, but cannot identify or exclude a polygenic model. In conclusion, two types of segregation analyses rejected a recessive model and favoured a dominant model of inheritance, although they could not statistically show that this fitted better than the polygenic model. The results raised the possibility of a common dominant gene with incomplete penetrance, but genetic analysis of NIDDM needs to take into account the likelihood of polygenic inheritance with genetic heterogeneity.Abbreviations MODY
Maturity onset diabetes of the young
- IDDM
insulin-dependent diabetes mellitus
- NIDDM
non-insulin-dependent diabetes mellitus
- FPG
fasting plasma glucose
- AIC
Akaike Information criterion 相似文献