全文获取类型
收费全文 | 807篇 |
免费 | 49篇 |
国内免费 | 29篇 |
专业分类
885篇 |
出版年
2024年 | 3篇 |
2023年 | 29篇 |
2022年 | 13篇 |
2021年 | 38篇 |
2020年 | 36篇 |
2019年 | 36篇 |
2018年 | 32篇 |
2017年 | 26篇 |
2016年 | 50篇 |
2015年 | 34篇 |
2014年 | 48篇 |
2013年 | 34篇 |
2012年 | 22篇 |
2011年 | 33篇 |
2010年 | 23篇 |
2009年 | 29篇 |
2008年 | 33篇 |
2007年 | 31篇 |
2006年 | 36篇 |
2005年 | 38篇 |
2004年 | 23篇 |
2003年 | 26篇 |
2002年 | 21篇 |
2001年 | 23篇 |
2000年 | 21篇 |
1999年 | 13篇 |
1998年 | 9篇 |
1997年 | 13篇 |
1996年 | 5篇 |
1995年 | 7篇 |
1994年 | 5篇 |
1993年 | 12篇 |
1992年 | 6篇 |
1991年 | 11篇 |
1990年 | 5篇 |
1989年 | 4篇 |
1988年 | 8篇 |
1987年 | 5篇 |
1986年 | 4篇 |
1985年 | 3篇 |
1984年 | 4篇 |
1983年 | 3篇 |
1982年 | 4篇 |
1981年 | 2篇 |
1980年 | 5篇 |
1979年 | 6篇 |
1978年 | 4篇 |
1977年 | 6篇 |
1976年 | 2篇 |
1973年 | 1篇 |
排序方式: 共有885条查询结果,搜索用时 0 毫秒
91.
Simon JS Karnoub MC Devlin DJ Arreaza MG Qiu P Monks SA Severino ME Deutsch P Palmisano J Sachs AB Bayne ML Plump AS Schadt EE 《Genomics》2005,86(6):648-656
Niemann-Pick C1-like 1 (NPC1L1) is an intestinal cholesterol transporter and the molecular target of ezetimibe, a cholesterol absorption inhibitor demonstrated to reduce LDL-cholesterol (LDL-C) both as monotherapy and when co-administered with 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins). Interestingly, significant interindividual variability has been observed for rates of intestinal cholesterol absorption and LDL-C reductions at both baseline and post ezetimibe treatment. To test the hypothesis that genetic variation in NPC1L1 could influence the LDL-C response to ezetimibe, we performed extensive resequencing of the gene in 375 apparently healthy individuals and genotyped hypercholesterolemic patients from clinical trial cohorts. No association was observed between NPC1L1 single-nucleotide polymorphism and baseline cholesterol. However, significant associations to LDL-C response to treatment with ezetimibe were observed in patients treated with ezetimibe in two large clinical trials. Our data demonstrate that DNA sequence variants in NPC1L1 are associated with an improvement in response to ezetimibe pharmacotherapy and suggest that detailed analysis of genetic variability in clinical trial cohorts can lead to improved understanding of factors contributing to variable drug response. 相似文献
92.
Hugo Asselin Serge Payette Marie-Josée Fortin Sheila Vallée 《Journal of Biogeography》2003,30(11):1709-1718
Aim Present northern distribution limit of jack pine (Pinus banksiana Lamb.) follows the northern limit of continuous open boreal forest in western Canada, but not in eastern Canada where it is located further south. We tested the hypothesis that fire plays a more important role than climate in explaining the present position of the northern distribution limit of jack pine. Location An experimental jack pine plantation was set up in 1992, c. 300 km north of the present distribution limit of the species, in the Boniface river area of northern Québec (57°43′ N, 76°05′ W). Methods Climate and fire data were used to compare sites at and north of the present distribution limit of jack pine. In 2001, surviving individuals from the plantation were measured (total height, annual shoot elongation, basal diameter, and presence/absence of cones). Results Climate data from the ten weather stations used in this study did not show major differences. The northern limit of jack pine distribution is closely associated with the occurrence of fires larger than 200 ha. Survival of the planted jack pines was 31%. About 25% of the surviving pines qualified as normal, single‐stem individuals; the others were slightly uprooted and/or showed marks of erosion or foraging. Cones were produced, although no viable seeds were found. Main conclusions The low number of degree‐days above 5 °C at the plantation site could explain why the seeds were not viable. However, such climate conditions are not sufficient to prevent growth, as was shown by annual shoot elongation measurements. Most of the surviving jack pines from the Boniface river plantation are relatively healthy and follow a normal developmental programme. Low fire frequency and small fire size are amongst the main factors that prevented P. banksiana from migrating further north or east following deglaciation in northern Québec and Labrador. 相似文献
93.
Clinical trials involve multi-site heterogeneous data generation with complex data input-formats and forms. The data should be captured and queried in an integrated fashion to facilitate further analysis. Electronic case-report forms (eCRF) are gaining popularity since it allows capture of clinical information in a rapid manner. We have designed and developed an XML based flexible clinical trials data management framework in .NET environment that can be used for efficient design and deployment of eCRFs to efficiently collate data and analyze information from multi-site clinical trials. The main components of our system include an XML form designer, a Patient registration eForm, reusable eForms, multiple-visit data capture and consolidated reports. A unique id is used for tracking the trial, site of occurrence, the patient and the year of recruitment.
Availability 相似文献
94.
Vera Lucia Portal Melissa Medeiros Markoski Alexandre Schaan de Quadros Sílvia Garofallo Julia Lorenzon dos Santos Aline Oliveira Camila Wechenfelder Viviane Paiva de Campos Priscilla Azambuja Lopes de Souza Luana Machado Aline Marcadenti 《Trials》2016,17(1)
BackgroundCardiovascular disease has become a major health problem, and it has been associated with both environmental and genetic factors. Studies have shown that the Mediterranean Diet (MeDiet), or its components such as nuts and olive oil, may be strongly associated with the improvement of cardiovascular risk factors in specific populations. The purpose of the GENUTRI study is to investigate the interaction of genetics with cardiovascular risk factors in a non-Mediterranean population with coronary artery disease (CAD) according to three different diets: rich in pecan nuts, in extra-virgin olive oil or a control diet.Methods/designThe GENUTRI study is a single-center, randomized, open-label, parallel-group, 12-week pragmatic clinical trial conducted in patients aged 40 to 80 years and diagnosed with CAD. A standardized questionnaire will be applied to data collection and a blood sample will be obtained for lipid, glycemic and inflammatory profile evaluation. Polymorphisms in the CD36 and STAT3 genes will be detected using the TaqMan® SNP Genotyping Assay. Patients will be allocated in three groups: group 1: 30 g/day of pecan nuts; group 2: 30 ml/day of olive oil; and group 3: control diet. The primary outcome will consist of changes in LDL-cholesterol (in mg/dl) after 12 weeks of intervention.DiscussionStudies have shown the beneficial effects of diets rich in nuts and olive oil mainly in the Mediterranean population. GENUTRI is a clinical trial focusing on the effects of nuts or olive oil supplementation in Brazilian individuals. Additionally, we will try to demonstrate that genetic polymorphisms linked to cardiovascular disease may modulate the effects of different diets on biochemical and inflammatory markers among these subjects.
Trial registration
ClinicalTrials.gov Identifier: (registered on 18 July 2014: first version). NCT02202265相似文献95.
Buzzi S Rubboli D Buzzi G Buzzi AM Morisi C Pironi F 《Cancer immunology, immunotherapy : CII》2004,53(11):1041-1048
Purpose: Many years ago, diphtheria toxin (DT) showed antitumor activity in mice and in humans, but it was unclear whether this depended on the toxicity of the molecule only or on its strong inflammatory-immunological property as well. To deal with this open question, we planned to treat a group of cancer patients with cross-reacting material 197 (CRM197). CRM197 is a nontoxic mutant of DT that shares the immunological properties of the native molecule and its ability to bind to heparin-binding epidermal growth factor (HB-EGF), the specific cell-membrane receptor for DT that is often overexpressed in cancer. Methods: 25 outpatients with various advanced tumors who were refractory to standard therapies (23 subjects) or had refused, in whole or in part, conventional therapies (2 subjects) were treated with CRM197 injected subcutaneously in the abdominal wall, on alternate days, for 6 days. Three different dosages (1.7, 2.6, or 3.5 mg/day) were used according to the patients degree of immunological reactivity to DT/CRM197 (none, moderate, or high). Results: After the first administration of CRM197, a significant increase in the number of circulating neutrophils and in the serum level of TNF- was detected. Toxicities were minimal. Only patients with delayed-type hypersensitivity to DT/CRM197 had irritating skin reactions in the injection sites and a flu-like syndrome with fever. Pharmacokinetics showed a mean peak concentration (12.7 ng/ml) 12 h after the first injection and a mean half-life of 18.1 h. There were two complete and one partial responses (metastatic breast carcinoma, neuroblastoma, and metastatic breast carcinoma) lasting 4, 45+, and 15 months, respectively. Six cases of stable disease, lasting from 1 to 15 months, were also recorded. Conclusions: CRM197 injected subcutaneously elicited an inflammatory-immunological reaction, caused tolerable toxicities, was absorbed to a good extent into the circulatory system, and exerted some degree of biological antitumor activity. A possible role of neutrophils and TNF- in the mode of action of the molecule is hypothesized. 相似文献
96.
In bioequivalence trials, one often considers two or more generic products with the original one. The 3 x 3 crossover design can be adopted to evaluate the two generic candidates with a brand name drug, rather than conducting two separate 2 x 2 crossover trials. Dropouts, however, are more likely to occur due to various administrative reasons when we consider a higher order crossover design. A modified method, which was originally given by Chow and Shao (1997), is extended to compare two generic products with a reference in the incomplete 3 x 3 crossover design. A simulation study and discussion are also presented. 相似文献
97.
O'Quigley J 《Biometrics》2005,61(3):749-756
The continual reassessment method (CRM) is a dose-finding design using a dynamic sequential updating scheme. In common with other dynamic schemes the method estimates a current dose level corresponding to some target percentile for experimentation. The estimate is based on all included subjects. This continual reevaluation is made possible by the use of a simple model. As it stands, neither the CRM, nor any of the other dynamic schemes, allow for the correct estimation of some target percentile, based on retrospective data apart from the exceptional situation in which the simplified model exactly generates the observations. In this article we focus on the very specific issue of retrospective analysis of data generated by some arbitrary mechanism and subsequently analyzed via the continual reassessment method. We show how this can be done consistently. The proposed methodology is not restricted to that particular design and is applicable to any sequential updating scheme in which dose levels are associated with percentiles via model inversion. 相似文献
98.
First-order intrinsic autoregressions and the de Wijs process 总被引:1,自引:0,他引:1
99.
A randomised controlled trial to evaluate a training programme for physician-patient communication required the analysis of paired count data. The impact of departures from the Poisson assumption when paired count data are analysed through use of a conditional likelihood is illustrated. A simple approach to providing robust inference is outlined and illustrated. 相似文献
100.
Effects of culling on badger Meles meles spatial organization: implications for the control of bovine tuberculosis 总被引:5,自引:2,他引:3