全文获取类型
收费全文 | 745篇 |
免费 | 119篇 |
国内免费 | 13篇 |
专业分类
儿科学 | 17篇 |
妇产科学 | 6篇 |
基础医学 | 128篇 |
口腔科学 | 9篇 |
临床医学 | 44篇 |
内科学 | 145篇 |
皮肤病学 | 22篇 |
神经病学 | 53篇 |
特种医学 | 2篇 |
外科学 | 37篇 |
综合类 | 32篇 |
现状与发展 | 1篇 |
预防医学 | 264篇 |
眼科学 | 21篇 |
药学 | 43篇 |
中国医学 | 13篇 |
肿瘤学 | 40篇 |
出版年
2024年 | 27篇 |
2023年 | 101篇 |
2022年 | 94篇 |
2021年 | 106篇 |
2020年 | 62篇 |
2019年 | 49篇 |
2018年 | 38篇 |
2017年 | 37篇 |
2016年 | 27篇 |
2015年 | 31篇 |
2014年 | 27篇 |
2013年 | 40篇 |
2012年 | 19篇 |
2011年 | 26篇 |
2010年 | 22篇 |
2009年 | 15篇 |
2008年 | 31篇 |
2007年 | 15篇 |
2006年 | 13篇 |
2005年 | 16篇 |
2004年 | 6篇 |
2003年 | 8篇 |
2002年 | 12篇 |
2001年 | 5篇 |
2000年 | 5篇 |
1999年 | 6篇 |
1998年 | 3篇 |
1997年 | 3篇 |
1996年 | 4篇 |
1995年 | 6篇 |
1994年 | 4篇 |
1993年 | 1篇 |
1992年 | 3篇 |
1989年 | 2篇 |
1988年 | 3篇 |
1987年 | 3篇 |
1985年 | 1篇 |
1984年 | 4篇 |
1982年 | 1篇 |
1981年 | 1篇 |
排序方式: 共有877条查询结果,搜索用时 15 毫秒
81.
《Nutrition, metabolism, and cardiovascular diseases : NMCD》2022,32(3):605-615
Background and aimsWhile low-density lipoprotein cholesterol (LDL-C) is a good predictor of atherosclerotic cardiovascular disease, apolipoprotein B (ApoB) is superior when the two markers are discordant. We aimed to determine the impact of adiposity, diet and inflammation upon ApoB and LDL-C discordance.Methods and resultsMachine learning (ML) and structural equation models (SEMs) were applied to the National Health and Nutrition Examination Survey to investigate cardiometabolic and dietary factors when LDL-C and ApoB are concordant/discordant. Mendelian randomisation (MR) determined whether adiposity and inflammation exposures were causal of elevated/decreased LDL-C and/or ApoB. ML showed body mass index (BMI), dietary saturated fatty acids (SFA), dietary fibre, serum C-reactive protein (CRP) and uric acid were the most strongly associated variables (R2 = 0.70) in those with low LDL-C and high ApoB. SEMs revealed that fibre (b = ?0.42, p = 0.001) and SFA (b = 0.28, p = 0.014) had a significant association with our outcome (joined effect of ApoB and LDL-C). BMI (b = 0.65, p = 0.001), fibre (b = ?0.24, p = 0.014) and SFA (b = 0.26, p = 0.032) had significant associations with CRP. MR analysis showed genetically higher body fat percentage had a significant causal effect on ApoB (Inverse variance weighted (IVW) = Beta: 0.172, p = 0.0001) but not LDL-C (IVW = Beta: 0.006, p = 0.845).ConclusionOur data show increased discordance between ApoB and LDL-C is associated with cardiometabolic, clinical and dietary abnormalities and that body fat percentage is causal of elevated ApoB. 相似文献
82.
A new method for isolating colonocytes from naturally evacuated feces and its clinical application to colorectal cancer diagnosis 总被引:6,自引:0,他引:6
Matsushita H Matsumura Y Moriya Y Akasu T Fujita S Yamamoto S Onouchi S Saito N Sugito M Ito M Kozu T Minowa T Nomura S Tsunoda H Kakizoe T 《Gastroenterology》2005,129(6):1918-1927
BACKGROUND & AIMS: The early detection of colorectal cancer is desired because this cancer can be cured surgically if diagnosed early. The purpose of the present study was to determine the feasibility of a new methodology for isolating colonocytes from naturally evacuated feces, followed by cytology or molecular biology of the colonocytes to detect colorectal cancer originating from any part of the colorectum. METHODS: Several simulation studies were conducted to establish the optimal methods for retrieving colonocytes from any portion of feces. Colonocytes exfoliated into feces, which had been retrieved from 116 patients with colorectal cancer and 83 healthy volunteers, were analyzed. Part of the exfoliated colonocytes was examined cytologically, whereas the remainder was subjected to DNA analysis. The extracted DNA was examined for mutations of the APC, K-ras, and p53 genes using direct sequence analysis and was also subjected to microsatellite instability (MSI) analysis. RESULTS: In the DNA analysis, the overall sensitivity and specificity were 71% (82 of 116) of patients with colorectal cancer and 88% (73 of 83) of healthy volunteers. The sensitivity for Dukes A and B was 72% (44 of 61). Furthermore, the sensitivity for cancers on the right side of the colon was 57% (20 of 35). The detection rate for genetic alterations using our methodology was 86% (80 of 93) when the analysis was limited to cases in which genetic alterations were present in the cancer tissue. CONCLUSIONS: We have developed a new methodology for isolating colonocytes from feces. The present study describes a promising procedure for future clinical evaluations and the early detection of colorectal cancers, including right-side colon cancer. 相似文献
83.
Martin L. Lesser 《Statistics in medicine》1982,1(3):277-280
Equal allocation of patients to treatment in a randomized clinical trial may have disadvantages ethically if the new treatment is believed to be at least as beneficial as the standard treatment. Others have considered, in a non-sequential setting, unbalanced randomized designs which allocate fewer patients to the potentially inferior standard treatment. This paper examines unbalanced randomized designs in a sequential comparison of two exponential survival distributions using the progressively censored Savage test. The results reveal no substantial sacrifice in asymptotic power or early stopping properties. 相似文献
84.
Toshiaki TACHIBANA 《Congenital anomalies》1984,24(1):55-62
The implausibility of random sampling assumption in experimental teratology is pointed out. It is emphasized that nonstatistical inference remains a standard scientific approach, in spite of widespread use of many statistical tests. The randomization test can be introduced to experimental teratologjsts as an alternative to conventional statistical procedures for nonrandom sampling data. A program list for the randomization test written in BASIC for microcompter is given. 相似文献
85.
John Ludbrook 《Clinical and experimental pharmacology & physiology》1994,21(9):673-686
1. The statistical procedures that are used most commonly in clinical and experimental pharmacology and physiology are designed to test for differences between two means. 2. The classical procedures for detecting such differences are those in which, under the population model of inference, the test statistic is referred to the t- or F-distributions. The validity of statistical inferences from these tests depends on a number of assumptions. Foremost among these is that the experimental groups have been constructed by taking random samples from defined populations. The statistical inferences then apply to the sampled populations. 3. In biomedical research this sampling process is seldom followed. Instead, samples are usually acquired by non-random selection, and are then divided by randomization into experimental groups. This being the case, it is theoretically invalid to use the classical t- or F-tests to analyse the experimental results. 4. The validity of inferences from the classical tests also depends on other assumptions, such as that the sampled populations are normal in form and of equal variance. It is difficult to be certain that these assumptions are fulfilled when group sizes are small, as they usually are in pharmacology and physiology. Breach of them, especially if the groups are unequal in size, can lead to serious statistical errors. 5. Exact permutation tests are designed to make statistical inferences under the randomization model. These conclusions apply only to the results of experiments actually performed. By permuting the statistic of interest, such as the difference between arithmetic means, geometric means, medians, mid-ranges or mean-ranks of randomized groups of observations, the probability is calculated that the observed difference or a more extreme one could have occurred by chance. This inferential process is consistent with the way most biomedical experiments are designed and conducted. 6. Exact permutation tests, or sampled permutation tests based on Monte Carlo random sampling of all possible permutations, can now be performed on personal computers. They are commended to biomedical investigators as being superior to the classical tests for analysing their experimental results when the central tendencies of two independent groups, or of two sets of measurements on the same group, are compared. 7. When there is doubt that the assumptions for t-tests are satisfied, investigators sometimes use non-parametric rank-order procedures such as the Wilcoxon-Mann-Whitney rank-sum test for independent groups or the Wilcoxon signed rank-sum test for paired observations. These procedures are permutation tests for differences between mean-ranks and are invalid tests for differences between medians or means. 8. When experiments are complex and based on randomization rather than random sampling, as in randomized block, Latin square, factorial or split-unit designs, analysis of these by permutation tests is to be preferred on theoretical grounds, though the necessary computer software is not readily available. 相似文献
86.
Betina Heinsbaek Thuesen Lise Lotte Nystrup Husemoen Mogens Fenger Allan Linneberg 《The clinical respiratory journal》2009,3(2):102-108
Background: Impaired folate metabolism has been suggested as a potential risk factor for the development of asthma and atopic disease. However, there have been conflicting reports on the potential association between atopic disease and a common polymorphism of the methylene‐tetrahydrofolate reductase (MTHFR)‐gene, a well‐known marker of impaired folate metabolism. Objectives: The aim of this study was to investigate the association between the MTHFR (C677T) polymorphism and different outcome variables of asthma and atopic disease. Methods: This study was a population‐based study of 1189 participants aged 15–77 years living in Copenhagen, the Capital of Denmark. Examinations included measurements of specific IgE and skin prick tests against inhalant allergens, metacholine bronchial hyper‐reactivity, and serum eosinophilic cationic protein, and a self‐administered questionnaire about diagnoses and symptoms of allergy and asthma. In addition, participants were genotyped for the MTHFR (C677T) polymorphism. Results: None of the examined outcomes were significantly associated with the MTHFR (C677T) polymorphism. Conclusions: The results of this study using detailed objective markers of atopic disease do not support the hypothesis that impaired folate metabolism as reflected by the MTHFR genotype is involved in the development of atopic disease. Please cite this paper as: Thuesen BH, Husemoen LLN, Fenger M and Linneberg A. Lack of association between the MTHFR (C677T) polymorphism and atopic disease. The Clinical Respiratory Journal 2009; 3: 102–108. 相似文献
87.
Florian B. Lagler Søren W. Gersting Clemens Zsifkovits Anna Eichinger Michael Staudigl Hartmut Glossmann 《Biochemical pharmacology》2010,80(10):1563-1571
Phenylketonuria (PKU), an autosomal recessive disease with phenylalanine hydroxylase (PAH) deficiency, was recently shown to be a protein misfolding disease with loss-of-function. It can be treated by oral application of the natural PAH cofactor tetrahydrobiopterin (BH4) that acts as a pharmacological chaperone and rescues enzyme function in vivo. Here we identified Pahenu1/2 bearing a mild and a severe mutation (V106A/F363S) as a new mouse model for compound heterozygous mild PKU. Although BH4 treatment has become established in clinical routine, there is substantial lack of knowledge with regard to BH4 pharmacodynamics and the effect of the genotype on the response to treatment with the natural cofactor. To address these questions we applied an elaborate methodological setup analyzing: (i) blood phenylalanine elimination, (ii) blood phenylalanine/tyrosine ratios, and (iii) kinetics of in vivo phenylalanine oxidation using 13C-phenylalanine breath tests. We compared pharmacodynamics in wild-type, Pahenu1/1, and Pahenu1/2 mice and observed crucial differences in terms of effect size as well as effect kinetics and dose response. Results from in vivo experiments were substantiated in vitro after overexpression of wild-type, V106A, and F263S in COS-7 cells. Pharmacokinetics did not differ between Pahenu1/1 and Pahenu1/2 indicating that the differences in pharmacodynamics were not induced by divergent pharmacokinetic behavior of BH4. In conclusion, our findings show a significant impact of the genotype on the response to BH4 in PAH deficient mice. This may lead to important consequences concerning the diagnostic and therapeutic management of patients with PAH deficiency underscoring the need for individualized procedures addressing pharmacodynamic aspects. 相似文献
88.
Mutations in the DFNB1 locus, where two connexin genes are located (GJB2 and GJB6), account for half of congenital cases of nonsyndromic autosomal recessive deafness. Because of the high frequency of DFNB1 gene mutations and the availability of genetic diagnostic tests involving these genes, they are the best candidates to develop a risk prediction model of being hearing impaired. People undergoing genetic counseling are normally interested in knowing the probability of having a hearing impaired child given his/her family history. To address this, a Mendelian model that predicts the probability of being a carrier of DFNB1 mutations, using family history of deafness, has been developed. This probability will be useful as additional information to decide whether or not a genetic test should be performed. This model incorporates Mendelian mode of inheritance, the age of onset of the disease, and the current age of hearing family members. The carrier probabilities are obtained using Bayes' theorem, in which mutation prevalence is used as the prior distribution. We have validated our model by using information from 305 families affected with congenital or progressive nonsyndromic deafness, in which genetic analysis of GJB2 and GJB6 had already been performed. This model works well, especially in homozygous carriers, showing a high discriminative power. This indicates that our proposed model can be useful in the context of clinical counseling of autosomal recessive disorders. 相似文献
89.
A well‐designed pilot study can advance science by providing essential preliminary data to support or motivate further research, refine study logistics, and demonstrate proof of concept. Often, the outcomes of such studies can be quantified by a success/failure dichotomy. For example, a novel compound may show activation of a neural pathway, or it may not. When an intervention''s efficacy is quantified using a dichotomous outcome, probability mass functions can be enumerated to determine the probability that the observed result from a pilot study supports further evaluation of the intervention since there is only a finite, and often small, number of sample configurations possible. The purpose of this research was to determine the probability of an “efficacy signal” for pilot studies using one‐ and two‐sample pilot study designs. Efficacy signal was defined as the probability of observing a more favorable response proportion relative to a historical control (one‐sample setting) or to a concurrent control (two‐sample setting). An enumeration study (exact simulation) was conducted to calculate the efficacy signal probability. One‐sample study designs yielded higher probability of determining an efficacy signal than the two‐sample setting; however, sampling variation must be accounted for. A 68% score confidence interval is recommended for this purpose. 相似文献
90.
《Statistics In Biopharmaceutical Research》2013,5(3):310-318
A fundamental question in response–adaptive randomization is: What allocation proportion should we target to achieve required power while resulting in fewer treatment failures? For comparing two treatments, such optimal allocations are well studied in the literature. However, few authors address the question for multiple treatments and the generalization of optimal allocations is necessary in practice. We are interested in finding the optimal allocation proportion, which achieves a required power of a multivariate test of homogeneity in binary response experiments while minimizing expected treatment failures at the same time. We propose such an optimal allocation for three treatments by giving an analytical solution for the optimization problem. Numerical studies show that a response–adaptive randomization procedure that targets proposed optimal allocation is superior to complete randomization. We also discuss some future research topics and additional issues on optimal adaptive designs. 相似文献