全文获取类型
收费全文 | 27306篇 |
免费 | 2290篇 |
国内免费 | 12篇 |
专业分类
29608篇 |
出版年
2023年 | 114篇 |
2022年 | 255篇 |
2021年 | 420篇 |
2020年 | 274篇 |
2019年 | 363篇 |
2018年 | 459篇 |
2017年 | 419篇 |
2016年 | 639篇 |
2015年 | 1181篇 |
2014年 | 1329篇 |
2013年 | 1625篇 |
2012年 | 1968篇 |
2011年 | 2036篇 |
2010年 | 1341篇 |
2009年 | 1169篇 |
2008年 | 1562篇 |
2007年 | 1656篇 |
2006年 | 1508篇 |
2005年 | 1535篇 |
2004年 | 1437篇 |
2003年 | 1243篇 |
2002年 | 1192篇 |
2001年 | 343篇 |
2000年 | 271篇 |
1999年 | 324篇 |
1998年 | 361篇 |
1997年 | 225篇 |
1996年 | 186篇 |
1995年 | 180篇 |
1994年 | 186篇 |
1993年 | 169篇 |
1992年 | 180篇 |
1991年 | 167篇 |
1990年 | 150篇 |
1989年 | 167篇 |
1988年 | 125篇 |
1987年 | 146篇 |
1986年 | 122篇 |
1985年 | 145篇 |
1984年 | 135篇 |
1983年 | 132篇 |
1982年 | 151篇 |
1981年 | 132篇 |
1980年 | 102篇 |
1979年 | 98篇 |
1978年 | 90篇 |
1977年 | 100篇 |
1976年 | 78篇 |
1974年 | 94篇 |
1973年 | 80篇 |
排序方式: 共有10000条查询结果,搜索用时 0 毫秒
991.
992.
Native to Southeast Asia, Drosophila suzukii (Matsumura) is a recent invader that infests intact ripe and ripening fruit, leading to significant crop losses in the U.S., Canada, and Europe. Since current D. suzukii management strategies rely heavily on insecticide usage and insecticide detoxification gene expression is under circadian regulation in the closely related Drosophila melanogaster, we set out to determine if integrative analysis of daily activity patterns and detoxification gene expression can predict chronotoxicity of D. suzukii to insecticides. Locomotor assays were performed under conditions that approximate a typical summer or winter day in Watsonville, California, where D. suzukii was first detected in North America. As expected, daily activity patterns of D. suzukii appeared quite different between ‘summer’ and ‘winter’ conditions due to differences in photoperiod and temperature. In the ‘summer’, D. suzukii assumed a more bimodal activity pattern, with maximum activity occurring at dawn and dusk. In the ‘winter’, activity was unimodal and restricted to the warmest part of the circadian cycle. Expression analysis of six detoxification genes and acute contact bioassays were performed at multiple circadian times, but only in conditions approximating Watsonville summer, the cropping season, when most insecticide applications occur. Five of the genes tested exhibited rhythmic expression, with the majority showing peak expression at dawn (ZT0, 6am). We observed significant differences in the chronotoxicity of D. suzukii towards malathion, with highest susceptibility at ZT0 (6am), corresponding to peak expression of cytochrome P450s that may be involved in bioactivation of malathion. High activity levels were not found to correlate with high insecticide susceptibility as initially hypothesized. Chronobiology and chronotoxicity of D. suzukii provide valuable insights for monitoring and control efforts, because insect activity as well as insecticide timing and efficacy are crucial considerations for pest management. However, field research is necessary for extrapolation to agricultural settings. 相似文献
993.
Detection of the lethal amphibian fungus Batrachochytrium dendrobatidis relies on PCR-based techniques. Although highly accurate and sensitive, these methods fail to distinguish between viable and dead cells. In this study a novel approach combining the DNA intercalating dye ethidium monoazide (EMA) and real-time PCR is presented that allows quantification of viable B. dendrobatidis cells without the need for culturing. The developed method is able to suppress real-time PCR signals of heat-killed B. dendrobatidis zoospores by 99.9 % and is able to discriminate viable from heat-killed B. dendrobatidis zoospores in mixed samples. Furthermore, the novel approach was applied to assess the antifungal activity of the veterinary antiseptic F10® Antiseptic Solution. This disinfectant killed B. dendrobatidis zoospores effectively within 1 min at concentrations as low as 1:6400. 相似文献
994.
Rationale
Screening and treating newly arriving immigrants for latent tuberculosis infection (LTBI) in low-incidence countries could be promising to reduce the tuberculosis incidence among this population. The effectiveness of screening with the tuberculin skin test (TST) is unknown.Objectives
To estimate the risk of progression to tuberculosis within two years after entry, stratified by TST result at entry.Methods
In a case-base design, we determined the prevalence of TST positives (10 mm and 15 mm) among a representative cohort of immunocompetent immigrants (n = 643) aged ≥18 years who arrived between April 2009 and March 2011 in the Netherlands (base cohort). Immigrants who progressed to tuberculosis within two years after arrival in 2005, 2006 or 2007 were extracted from the Netherlands Tuberculosis Register (case source cohort). The prevalence of TST positives from the base cohort was projected on the case source cohort to estimate the risk of progression to active tuberculosis by using Bayesian analyses to adjust for the sensitivity of the TST and Poisson regression analyses to take into account the random error of the number of extracted cases.Results
The prevalence of TST positives was 42% and 23% for a cut-off value of 10 mm and 15 mm, respectively. The overall risk of progression to tuberculosis if TST positive was 238 per 100,000 population (95% CI 151–343) and 295 per 100,000 population (95% CI 161–473) for a cut-off value of ≥10 mm and ≥15 mm, respectively. The corresponding risk for TST negatives was 19 (95% CI 0–59) and 58 (95% CI 25–103).Conclusion
The TST has the discriminatory ability to differentiate between individuals at low and high risk of disease. 相似文献995.
Yvonne Dzierma Frank G. Nuesken Jochen Fleckenstein Stephanie Kremp Norbert P. Licht Christian Ruebe 《PloS one》2013,8(1)
Respiratory motion during percutaneous radiotherapy can be considered based on respiration-correlated computed tomography (4DCT). However, most treatment planning systems perform the dose calculation based on a single primary CT data set, even though cine mode displays may allow for a visualisation of the complete breathing cycle. This might create the mistaken impression that the dose distribution were independent of tumour motion. We present a movie visualisation technique with the aim to direct attention to the fact that the dose distribution migrates to some degree with the tumour and discuss consequences for gated treatment, IMRT plans and flattening-filter-free beams. This is a feasibility test for a visualisation of tumour and isodose motion. Ten respiratory phases are distinguished on the CT, and the dose distribution from a stationary IMRT plan is calculated on each phase, to be integrated into a movie of tumour and dose motion during breathing. For one example patient out of the sample of five lesions, the plan is compared with a gated treatment plan with respect to tumour coverage and lung sparing. The interplay-effect for small segments in the IMRT plan is estimated. While the high dose rate, together with the cone-shaped beam profile, makes the use of flattening-filter-free beams more problematic for conformal and IMRT treatment, it can be the option of choice if gated treatment is preferred. The different effects of respiratory motion, dose build-up and beam properties (segments and flatness) for gated vs. un-gated treatment can best be considered if planning is performed on the full 4DCT data set, which may be an incentive for future developments of treatment planning systems. 相似文献
996.
Martin Neumann Ebru Coskun Lars Fransecky Liliana H. Mochmann Isabelle Bartram Nasrin Farhadi Sartangi Sandra Heesch Nicola G?kbuget Stefan Schwartz Christian Brandts Cornelia Schlee Rainer Haas Ulrich Dührsen Martin Griesshammer Hartmut D?hner Gerhard Ehninger Thomas Burmeister Olga Blau Eckhard Thiel Dieter Hoelzer Wolf-Karsten Hofmann Claudia D. Baldus 《PloS one》2013,8(1)
Early T-cell precursor acute lymphoblastic leukemia (ETP-ALL) has been identified as high-risk subgroup of acute T-lymphoblastic leukemia (T-ALL) with a high rate of FLT3-mutations in adults. To unravel the underlying pathomechanisms and the clinical course we assessed molecular alterations and clinical characteristics in a large cohort of ETP-ALL (n = 68) in comparison to non-ETP T-ALL adult patients. Interestingly, we found a high rate of FLT3-mutations in ETP-ALL samples (n = 24, 35%). Furthermore, FLT3 mutated ETP-ALL was characterized by a specific immunophenotype (CD2+/CD5-/CD13+/CD33-), a distinct gene expression pattern (aberrant expression of IGFBP7, WT1, GATA3) and mutational status (absence of NOTCH1 mutations and a low frequency, 21%, of clonal TCR rearrangements). The observed low GATA3 expression and high WT1 expression in combination with lack of NOTCH1 mutations and a low rate of TCR rearrangements point to a leukemic transformation at the pluripotent prothymocyte stage in FLT3 mutated ETP-ALL. The clinical outcome in ETP-ALL patients was poor, but encouraging in those patients with allogeneic stem cell transplantation (3-year OS: 74%). To further explore the efficacy of targeted therapies, we demonstrate that T-ALL cell lines transfected with FLT3 expression constructs were particularly sensitive to tyrosine kinase inhibitors. In conclusion, FLT3 mutated ETP-ALL defines a molecular distinct stem cell like leukemic subtype. These data warrant clinical studies with the implementation of FLT3 inhibitors in addition to early allogeneic stem cell transplantation for this high risk subgroup. 相似文献
997.
Ludovic Reveiz Stephanie Sangalang Demian Glujovsky Carlos E. Pinzon Claudia Asenjo Lobos Marcela Cortes Martin Ca?ón Ariel Bardach Xavier Bonfill 《PloS one》2013,8(2)
Introduction
Few studies have assessed the nature and quality of randomized controlled trials (RCTs) in Latin America and the Caribbean (LAC).Methods and Findings
The aims of this systematic review are to evaluate the characteristics (including the risk of bias assessment) of RCT conducted in LAC according to funding source. A review of RCTs published in 2010 in which the author''s affiliation was from LAC was performed in PubMed and LILACS. Two reviewers independently extracted data and assessed the risk of bias. The primary outcomes were risk of bias assessment and funding source. A total of 1,695 references were found in PubMed and LILACS databases, of which 526 were RCTs (N = 73.513 participants). English was the dominant publication language (93%) and most of the RCTs were published in non-LAC journals (84.2%). Only five of the 19 identified countries accounted for nearly 95% of all RCTs conducted in the region (Brazil 70.9%, Mexico 10.1%, Argentina 5.9%, Colombia 3.8%, and Chile 3.4%). Few RCTs covered priority areas related with Millennium Development Goals like maternal health (6.7%) or high priority infectious diseases (3.8%). Regarding children, 3.6% and 0.4% RCT evaluated nutrition and diarrhea interventions respectively but none pneumonia. As a comparison, aesthetic and sport related interventions account for 4.6% of all trials. A random sample of RCTs (n = 358) was assessed for funding source: exclusively public (33.8%); private (e.g. pharmaceutical company) (15.3%); other (e.g. mixed, NGO) (15.1%); no funding (35.8%). Overall assessments for risk of bias showed no statistically significant differences between RCTs and type of funding source. Statistically significant differences favoring private and others type of funding was found when assessing trial registration and conflict of interest reporting.Conclusion
Findings of this study could be used to provide more direction for future research to facilitate innovation, improve health outcomes or address priority health problems. 相似文献998.
999.
Ana Horta Claudia Nobrega Pedro Amorim-Machado Vitor Coutinho-Teixeira Palmira Barreira-Silva Susana Boavida Patrício Costa Rui Sarmento-Castro António Gil Castro Margarida Correia-Neves 《PloS one》2013,8(2)
CD4+ regulatory T cells (Tregs) are essential for the maintenance of the immune system''s equilibrium, by dampening the activation of potential auto-reactive T cells and avoiding excessive immune activation. To correctly perform their function, Tregs must be maintained at the right proportion with respect to effector T cells. Since this equilibrium is frequently disrupted in individuals infected with the human immunodeficiency virus (HIV), we hypothesize that its deregulation could hamper immune reconstitution in patients with poor CD4+ T cell recovery under highly active antiretroviral therapy (HAART). We analysed Tregs percentages amongst CD4+ T cells in 53 HIV-infected patients under HAART, with suppression of viral replication and distinct levels of immune reconstitution. As controls, 51 healthy individuals were also analysed. We observed that amongst the patients with Nadir values (the lowest CD4+ T cell counts achieved) <200 cells/µL, the individuals with high Tregs percentages (≥10% of total CD4+ T cells) had the worse CD4+ T cell reconstitution. In accordance, the well-described direct correlation between the Nadir value and CD4+ T cell reconstitution is clearly more evident in individuals with high Tregs proportions. Furthermore, we observed a strong negative correlation between Tregs percentages and CD4+ T cell recovery among immunological non-responder HIV+ individuals. All together, this work shows that high Tregs frequency is an important factor associated with sub-optimal CD4+ T cell recovery. This is particularly relevant for immunological non-responders with low Nadir values. Our results suggest that the Tregs proportion might be of clinical relevance to define cut-offs for HAART initiation. 相似文献
1000.
Vitantonio Di Bello Iacopo Fabiani Lorenzo Conte Valentina Barletta Maria Grazia Delle Donne Cucco Cuono Laura Anna Leo Frank Lloyd Dini Mario Marzilli Aldo Pinchera Ferruccio Santini 《Obesity (Silver Spring, Md.)》2013,21(5):881-892