全文获取类型
收费全文 | 2282篇 |
免费 | 133篇 |
国内免费 | 35篇 |
出版年
2023年 | 5篇 |
2022年 | 15篇 |
2021年 | 57篇 |
2020年 | 11篇 |
2018年 | 33篇 |
2017年 | 24篇 |
2016年 | 91篇 |
2015年 | 201篇 |
2014年 | 221篇 |
2013年 | 241篇 |
2012年 | 270篇 |
2011年 | 189篇 |
2010年 | 108篇 |
2009年 | 91篇 |
2008年 | 104篇 |
2007年 | 70篇 |
2006年 | 52篇 |
2005年 | 83篇 |
2004年 | 77篇 |
2003年 | 62篇 |
2002年 | 60篇 |
2001年 | 43篇 |
2000年 | 29篇 |
1999年 | 13篇 |
1998年 | 16篇 |
1997年 | 11篇 |
1996年 | 14篇 |
1994年 | 5篇 |
1993年 | 12篇 |
1992年 | 10篇 |
1991年 | 10篇 |
1990年 | 13篇 |
1989年 | 11篇 |
1988年 | 13篇 |
1986年 | 10篇 |
1985年 | 5篇 |
1983年 | 5篇 |
1982年 | 5篇 |
1978年 | 5篇 |
1974年 | 6篇 |
1973年 | 5篇 |
1972年 | 5篇 |
1968年 | 5篇 |
1962年 | 5篇 |
1961年 | 4篇 |
1960年 | 4篇 |
1957年 | 6篇 |
1951年 | 5篇 |
1947年 | 4篇 |
1926年 | 4篇 |
排序方式: 共有2450条查询结果,搜索用时 31 毫秒
171.
Smith JA van den Broek FA Martorell JC Hackbarth H Ruksenas O Zeller W;FELASA Working Group on Ethical Evaluation of Animal Experiments 《Laboratory animals》2007,41(2):143-160
This paper summarizes a more detailed report produced by the Federation of European Laboratory Animal Science Associations (FELASA 2005), which describes and explores a set of principles for the conduct of ethical review of laboratory animal use. It presents a synopsis of results from a questionnaire that elicited information on how each of 20 countries represented in FELASA currently approaches such ethical review. This information suggests that, although local practices differ, there is an emerging consensus on the key elements that any ethical review process should involve. Drawing on the questionnaire findings, this summary also includes a brief discussion to support and amplify a series of recommendations, covering the objectives of ethical review; legal requirements; the scope of work reviewed and the 'level' at which review is approached; general principles for the organization of ethical review processes; the factors considered in the review; needs for ongoing review after initial authorization; participants in the review process; wider impacts of the review process; and strategies that can help to ensure quality and consistency of review outcomes. For further information and examples of current practice, as well as more detailed discussion to support the recommendations, readers are urged to refer to the complete report, available at http://www.lal.org.uk/pdffiles/FELASA_ethics_FULL_Report. pdf or via: http://www.felasa.eu/recommendations.htm. 相似文献
172.
173.
174.
Hawkey CJ Talley NJ Scheiman JM Jones RH Långström G Naesdal J Yeomans ND;NASA/SPACE author group 《Arthritis research & therapy》2007,9(1):R17
Non-steroidal anti-inflammatory drugs (NSAIDs), including selective cyclo-oxygenase-2 (COX-2) inhibitors, cause upper gastrointestinal
(GI) symptoms that are relieved by treatment with esomeprazole. We assessed esomeprazole for maintaining long-term relief
of such symptoms. Six hundred and ten patients with a chronic condition requiring anti-inflammatory therapy who achieved relief
of NSAID-associated symptoms of pain, discomfort, or burning in the upper abdomen during two previous studies were enrolled
and randomly assigned into two identical, multicentre, parallel-group, placebo-controlled studies of esomeprazole 20 mg or
40 mg treatment (NASA2 [Nexium Anti-inflammatory Symptom Amelioration] and SPACE2 [Symptom Prevention by Acid Control with
Esomeprazole] studies; ClinicalTrials.gov identifiers NCT00241514 and NCT00241553, respectively) performed at various rheumatology,
gastroenterology, and primary care clinics. Four hundred and twenty-six patients completed the 6-month treatment period. The
primary measure was the proportion of patients with relapse of upper GI symptoms, recorded in daily diary cards, after 6 months.
Relapse was defined as moderate-to-severe upper GI symptoms (a score of more than or equal to 3 on a 7-grade scale) for 3
days or more in any 7-day period. Esomeprazole was significantly more effective than placebo in maintaining relief of upper
GI symptoms throughout 6 months of treatment. Life-table estimates (95% confidence intervals) of the proportion of patients
with relapse at 6 months (pooled population) were placebo, 39.1% (32.2% to 46.0%); esomeprazole 20 mg, 29.3% (22.3% to 36.2%)
(p = 0.006 versus placebo); and esomeprazole 40 mg, 26.1% (19.4% to 32.9%) (p = 0.001 versus placebo). Patients on either non-selective NSAIDs or selective COX-2 inhibitors appeared to benefit. The frequency
of adverse events was similar in the three groups. Esomeprazole maintains relief of NSAID-associated upper GI symptoms in
patients taking continuous NSAIDs, including selective COX-2 inhibitors. 相似文献
175.
Brain bank of the Brazilian aging brain study group—a milestone reached and more than 1,600 collected brains 总被引:2,自引:0,他引:2
Grinberg LT Ferretti RE Farfel JM Leite R Pasqualucci CA Rosemberg S Nitrini R Saldiva PH Filho WJ;Brazilian Aging Brain Study Group 《Cell and tissue banking》2007,8(2):151-162
INTRODUCTION: Brain banking remains a necessity for the study of aging brain processes and related neurodegenerative diseases. In the present paper, we report the methods applied at and the first results of the Brain Bank of the Brazilian Aging Brain Study Group (BBBABSG) which has two main aims: (1) To collect a large number of brains of elderly comprising non-demented subjects and a large spectrum of pathologies related to aging brain processes, (2) To provide quality material to a multidisciplinar research network unraveling multiple aspects of aging brain processes and related neurodegenerative diseases. METHODS: The subjects are selected from the Sao Paulo Autopsy Service. Brain parts are frozen and fixated. CSF, carotids, kidney, heart and blood are also collected and DNA is extracted. The neuropathological examinations are carried out based on accepted criteria, using immunohistochemistry. Functional status are assessed through a collateral source based on a clinical protocol. Protocols are approved by the local ethics committee and a written informed consent form is obtained. RESULTS: During the first 21 months, 1,602 samples were collected and were classified by Clinical Dementia Rating as CDR0: 65.7%; CDR0.5:12.6%, CDR1:8.2%, CDR2:5.4%, and CDR3:8.1%. On average, the cost for the processing each case stood at 400 US dollars. To date, 14 laboratories have been benefited by the BBBABSG. CONCLUSION: The high percentage of non- demented subjects and the ethnic diversity of this series may be significantly contributive toward aging brain processes and related neurodegenerative diseases understanding since BBBABSG outcomes may provide investigators the answers to some additional questions. 相似文献
176.
Elena Ciani Emiliano Lasagna Mariasilvia D’Andrea Ingrid Alloggio Fabio Marroni Simone Ceccobelli Juan V. Delgado Bermejo Francesca M. Sarti James Kijas Johannes A. Lenstra Fabio Pilla the International Sheep Genomics Consortium 《遗传、选种与进化》2015,47(1)
Background
Merino and Merino-derived sheep breeds have been widely distributed across the world, both as purebred and admixed populations. They represent an economically and historically important genetic resource which over time has been used as the basis for the development of new breeds. In order to examine the genetic influence of Merino in the context of a global collection of domestic sheep breeds, we analyzed genotype data that were obtained with the OvineSNP50 BeadChip (Illumina) for 671 individuals from 37 populations, including a subset of breeds from the Sheep HapMap dataset.Results
Based on a multi-dimensional scaling analysis, we highlighted four main clusters in this dataset, which corresponded to wild sheep, mouflon, primitive North European breeds and modern sheep (including Merino), respectively. The neighbor-network analysis further differentiated North-European and Mediterranean domestic breeds, with subclusters of Merino and Merino-derived breeds, other Spanish breeds and other Italian breeds. Model-based clustering, migration analysis and haplotype sharing indicated that genetic exchange occurred between archaic populations and also that a more recent Merino-mediated gene flow to several Merino-derived populations around the world took place. The close relationship between Spanish Merino and other Spanish breeds was consistent with an Iberian origin for the Merino breed, with possible earlier contributions from other Mediterranean stocks. The Merino populations from Australia, New Zealand and China were clearly separated from their European ancestors. We observed a genetic substructuring in the Spanish Merino population, which reflects recent herd management practices.Conclusions
Our data suggest that intensive gene flow, founder effects and geographic isolation are the main factors that determined the genetic makeup of current Merino and Merino-derived breeds. To explain how the current Merino and Merino-derived breeds were obtained, we propose a scenario that includes several consecutive migrations of sheep populations that may serve as working hypotheses for subsequent studies.Electronic supplementary material
The online version of this article (doi:10.1186/s12711-015-0139-z) contains supplementary material, which is available to authorized users. 相似文献177.
Devan Jaganath J Jaime Miranda Robert H Gilman Robert A Wise Gregory B Diette Catherine H Miele Antonio Bernabe-Ortiz William Checkley CRONICAS Cohort Study Group 《Respiratory research》2015,16(1)
Background
It is unclear how geographic and social diversity affects the prevalence of chronic obstructive pulmonary disease (COPD). We sought to characterize the prevalence of COPD and identify risk factors across four settings in Peru with varying degrees of urbanization, altitude, and biomass fuel use.Methods
We collected sociodemographics, clinical history, and post-bronchodilator spirometry in a randomly selected, age-, sex- and site-stratified, population-based sample of 2,957 adults aged ≥35 years (median age was 54.8 years and 49.3% were men) from four resource-poor settings: Lima, Tumbes, urban and rural Puno. We defined COPD as a post-bronchodilator FEV1/FVC < 70%.Results
Overall prevalence of COPD was 6.0% (95% CI 5.1%–6.8%) but with marked variation across sites: 3.6% in semi-urban Tumbes, 6.1% in urban Puno, 6.2% in Lima, and 9.9% in rural Puno (p < 0.001). Population attributable risks (PARs) of COPD due to smoking ≥10 pack-years were less than 10% for all sites, consistent with a low prevalence of daily smoking (3.3%). Rather, we found that PARs of COPD varied by setting. In Lima, for example, the highest PARs were attributed to post-treatment tuberculosis (16% and 22% for men and women, respectively). In rural Puno, daily biomass fuel for cooking among women was associated with COPD (prevalence ratio 2.22, 95% CI 1.02–4.81) and the PAR of COPD due to daily exposure to biomass fuel smoke was 55%.Conclusions
The burden of COPD in Peru was not uniform and, unlike other settings, was not predominantly explained by tobacco smoking. This study emphasizes the role of biomass fuel use, and highlights pulmonary tuberculosis as an often neglected risk factor in endemic areas. 相似文献178.
Innominato PF Giacchetti S Moreau T Smaaland R Focan C Bjarnason GA Garufi C Iacobelli S Tampellini M Tumolo S Carvalho C Karaboué A Lévi F;ARTBC International Chronotherapy Group 《Chronobiology international》2011,28(7):586-600
Circadian clocks control cellular proliferation and drug metabolism over the 24?h. However, circadian chronomodulated chemotherapy with 5-fluorouracil, leucovorin, and oxaliplatin (chronoFLO4) offered no survival benefit as compared with the non-time-stipulated FOLFOX2, in an international randomized trial involving patients with previously untreated metastatic colorectal cancer (EORTC 05963). The authors hypothesized that treatment near maximum tolerated dose could disrupt circadian clocks thus impairing the efficacy of chronoFLO4 but not of FOLFOX2. Patients with available data (N?=?556) were categorized into three subgroups according to the worst grade (G) of neutropenia experienced during treatment. Distinct multivariate models with time-dependent covariates were constructed for each treatment schedule. Neutropenia incidence (all grades) was 33% on chronoFLO4 and 61% on FOLFOX2 (p?.0001), and G3-4 were 7% and 25%, respectively (p < .0001). Neutropenia was significantly more frequent in women than men on either schedule (FOLFOX2, p = .003; chronoFLO4, p = .04). Median survival was 20.7 mo in patients with G3-4 neutropenia versus 12.5 mo in neutropenia-free patients on FOLFOX2 (p < .0001). Corresponding figures were 13.7 and 19.4 mo, respectively, on chronoFLO4 (p?=?.36). Multivariate analysis confirmed occurrence of severe neutropenia independently predicted for better overall survival on FOLFOX2 (HR?=?0.56; p = .015), and worse survival on chronoFLO4 (HR?=?1.77, p = .06), with a significant interaction test (p < .0001). Prediction of better survival in neutropenic patients on FOLFOX2 supports the administration of conventional chemotherapy near maximum tolerated dose. The opposite trend shown here for chronoFLO4 supports the novel concept of jointly optimized hematologic tolerability and efficacy through personalized circadian-timed therapy. 相似文献
179.
Lisa Langsetmo Tuan V. Nguyen Nguyen D. Nguyen Christopher S. Kovacs Jerilynn C. Prior Jacqueline R. Center Suzanne Morin Robert G. Josse Jonathan D. Adachi David A. Hanley John A. Eisman the Canadian Multicentre Osteoporosis Study Research Group 《CMAJ》2011,183(2):E107-E114
Background
A set of nomograms based on the Dubbo Osteoporosis Epidemiology Study predicts the five- and ten-year absolute risk of fracture using age, bone mineral density and history of falls and low-trauma fracture. We assessed the discrimination and calibration of these nomograms among participants in the Canadian Multicentre Osteoporosis Study.Methods
We included participants aged 55–95 years for whom bone mineral density measurement data and at least one year of follow-up data were available. Self-reported incident fractures were identified by yearly postal questionnaire or interview (years 3, 5 and 10). We included low-trauma fractures before year 10, except those of the skull, face, hands, ankles and feet. We used a Cox proportional hazards model.Results
Among 4152 women, there were 583 fractures, with a mean follow-up time of 8.6 years. Among 1606 men, there were 116 fractures, with a mean follow-up time of 8.3 years. Increasing age, lower bone mineral density, prior fracture and prior falls were associated with increased risk of fracture. For low-trauma fractures, the concordance between predicted risk and fracture events (Harrell C) was 0.69 among women and 0.70 among men. For hip fractures, the concordance was 0.80 among women and 0.85 among men. The observed fracture risk was similar to the predicted risk in all quintiles of risk except the highest quintile of women, where it was lower. The net reclassification index (19.2%, 95% confidence interval [CI] 6.3% to 32.2%), favours the Dubbo nomogram over the current Canadian guidelines for men.Interpretation
The published nomograms provide good fracture-risk discrimination in a representative sample of the Canadian population.Current recommendations for the treatment of osteoporosis are in transition. The T-score-based definition of osteoporosis and osteopenia by the expert committee of the World Health Organization on bone mineral density has been used in many guidelines to set intervention thresholds for treatment. However, studies have consistently reported that the highest number of fractures in a given population occurs in those with osteopenic or normal bone mineral density.1,2 In fact, the National Osteoporosis Foundation has singled out people with osteopenic bone mineral density as a population in which assessment for fracture risk is merited.3Nevertheless, appropriate prevention and treatment strategies for such people are uncertain.4 Recent developments include the assessment of absolute fracture risk based on bone mineral density and other risk factors. Current Canadian methodology determines categorical risk based on age, sex, T-score, fracture history and glucocorticoid use.5 These criteria were derived from Swedish data, but have been assessed and validated in a cohort of Manitoba women.6 Newer nomograms based on the Australian cohort of the Dubbo Osteoporosis Epidemiology Study7 are now available for the calculation of low-trauma hip fracture8 and any fracture.9 These nomograms provide continuous estimates for five- and 10-year absolute fracture risk in both men and women (available at http://fractureriskcalculator.com). The use of factors in addition to bone mineral density may provide a better assessment of fracture risk for people who are near the T-score thresholds and facilitate decisions regarding therapeutic intervention.A key step in the development of any prediction model is the assessment of its validity.10 The aim of our study was to assess the performance of the Australian-derived nomogram among community-dwelling Canadians aged 55–95 years old. The first part of this assessment was a comparison of the nomogram model using the same variables, but using data from a Canadian population — participants in the Canadian Multicentre Osteoporosis Study (www.camos.org). The second part involved computing the calibration and discrimination of the nomogram in a Canadian cohort. The final part was comparison of the new assessments with the existing Canadian risk classification system. 相似文献180.