全文获取类型
收费全文 | 2443篇 |
免费 | 178篇 |
出版年
2023年 | 14篇 |
2022年 | 36篇 |
2021年 | 60篇 |
2020年 | 40篇 |
2019年 | 63篇 |
2018年 | 80篇 |
2017年 | 52篇 |
2016年 | 96篇 |
2015年 | 150篇 |
2014年 | 140篇 |
2013年 | 184篇 |
2012年 | 238篇 |
2011年 | 231篇 |
2010年 | 124篇 |
2009年 | 117篇 |
2008年 | 145篇 |
2007年 | 141篇 |
2006年 | 107篇 |
2005年 | 90篇 |
2004年 | 96篇 |
2003年 | 95篇 |
2002年 | 82篇 |
2001年 | 12篇 |
2000年 | 14篇 |
1999年 | 19篇 |
1998年 | 27篇 |
1997年 | 23篇 |
1996年 | 12篇 |
1995年 | 9篇 |
1994年 | 16篇 |
1993年 | 9篇 |
1992年 | 16篇 |
1991年 | 8篇 |
1990年 | 5篇 |
1989年 | 6篇 |
1988年 | 3篇 |
1987年 | 6篇 |
1986年 | 5篇 |
1985年 | 7篇 |
1984年 | 6篇 |
1983年 | 4篇 |
1982年 | 5篇 |
1981年 | 5篇 |
1980年 | 2篇 |
1979年 | 4篇 |
1977年 | 2篇 |
1975年 | 3篇 |
1974年 | 2篇 |
1965年 | 1篇 |
1961年 | 2篇 |
排序方式: 共有2621条查询结果,搜索用时 15 毫秒
71.
Luis Fernández Luis Alejandro de Haro Ana J. Distefano Maria Carolina Martínez Verónica Lía Juan C. Papa Ignacio Olea Daniela Tosto Horacio Esteban Hopp 《Ecology and evolution》2013,3(10):3388-3400
Single sequence repeats (SSR) developed for Sorghum bicolor were used to characterize the genetic distance of 46 different Sorghum halepense (Johnsongrass) accessions from Argentina some of which have evolved toward glyphosate resistance. Since Johnsongrass is an allotetraploid and only one subgenome is homologous to cultivated sorghum, some SSR loci amplified up to two alleles while others (presumably more conserved loci) amplified up to four alleles. Twelve SSR providing information of 24 loci representative of Johnsongrass genome were selected for genetic distance characterization. All of them were highly polymorphic, which was evidenced by the number of different alleles found in the samples studied, in some of them up to 20. UPGMA and Mantel analysis showed that Johnsongrass glyphosate‐resistant accessions that belong to different geographic regions do not share similar genetic backgrounds. In contrast, they show closer similarity to their neighboring susceptible counterparts. Discriminant Analysis of Principal Components using the clusters identified by K‐means support the lack of a clear pattern of association among samples and resistance status or province of origin. Consequently, these results do not support a single genetic origin of glyphosate resistance. Nucleotide sequencing of the 5‐enolpyruvylshikimate‐3‐phosphate synthase (EPSPS) encoding gene from glyphosate‐resistant and susceptible accessions collected from different geographic origins showed that none presented expected mutations in aminoacid positions 101 and 106 which are diagnostic of target‐site resistance mechanism. 相似文献
72.
Gemma Navarro Estefania Moreno Jordi Bonaventura Marc Brugarolas Daniel Farré David Aguinaga Josefa Mallol Antoni Cortés Vicent Casadó Carmen Lluís Sergi Ferre Rafael Franco Enric Canela Peter J. McCormick 《PloS one》2013,8(4)
Under normal conditions the brain maintains a delicate balance between inputs of reward seeking controlled by neurons containing the D1-like family of dopamine receptors and inputs of aversion coming from neurons containing the D2-like family of dopamine receptors. Cocaine is able to subvert these balanced inputs by altering the cell signaling of these two pathways such that D1 reward seeking pathway dominates. Here, we provide an explanation at the cellular and biochemical level how cocaine may achieve this. Exploring the effect of cocaine on dopamine D2 receptors function, we present evidence of σ1 receptor molecular and functional interaction with dopamine D2 receptors. Using biophysical, biochemical, and cell biology approaches, we discovered that D2 receptors (the long isoform of the D2 receptor) can complex with σ1 receptors, a result that is specific to D2 receptors, as D3 and D4 receptors did not form heteromers. We demonstrate that the σ1-D2 receptor heteromers consist of higher order oligomers, are found in mouse striatum and that cocaine, by binding to σ1 -D2 receptor heteromers, inhibits downstream signaling in both cultured cells and in mouse striatum. In contrast, in striatum from σ1 knockout animals these complexes are not found and this inhibition is not seen. Taken together, these data illuminate the mechanism by which the initial exposure to cocaine can inhibit signaling via D2 receptor containing neurons, destabilizing the delicate signaling balance influencing drug seeking that emanates from the D1 and D2 receptor containing neurons in the brain. 相似文献
73.
Ignacio Pérez-Valero Alicia González-Baeza Miriam Estébanez María L. Montes-Ramírez Carmen Bayón Federico Pulido José I. Bernardino Francisco X. Zamora Susana Monge Francisco Gaya María Lagarde Rafael Rubio Asunción Hernando Francisco Arnalich José R. Arribas 《PloS one》2013,8(7)
Background
In patients who remain virologically suppressed in plasma with triple-drug ART a switch to protease inhibitor monotherapy maintains high rates of suppression; however it is unknown if protease inhibitor monotherapy is associated to a higher rate of neurocognitive impairment.Methods
In this observational, cross-sectional study we included patients with plasma virological suppression (≥1 year) without concomitant major neurocognitive confounders, currently receiving for ≥1 year boosted lopinavir or darunavir as monotherapy or as triple ART. Neurocognitive impairment was defined as per the 2007 consensus of the American Association of Neurology. The association between neurocognitive impairment and protease inhibitor monotherapy, adjusted by significant confounders, was analysed.Results
Of the 191 included patients - triple therapy: 96, 1–2 years of monotherapy: 40 and >2 years of monotherapy: 55 - proportions (95% CI) with neurocognitive impairment were: overall, 27.2% (20.9–33.6); triple therapy, 31.6% (22.1–41.0); short-term monotherapy, 25.0% (11.3–38.7); long-term monotherapy: 21.4% (10.5–32.3); p = 0.38. In all groups, neurocognitive impairment was mildly symptomatic or asymptomatic by self-report. There were not significant differences in Global Deficit Score by group. In the regression model confounding variables for neurocognitive impairment were years on ART, ethnicity, years of education, transmission category and the HOMA index. Adjusted by these variables the Odds Ratio (95% CI) for neurocognitive impairment of patients receiving short-term monotherapy was 0.85 (0.29–2.50) and for long-term monotherapy 0.40 (0.14–1.15).Conclusions
Compared to triple drug antiretroviral therapy, monotherapy with lopinavir/ritonavir or darunavir/ritonavir in patients with adequate plasma suppression was not associated with a higher rate of asymptomatic neurocognitive impairment than triple drug ART. 相似文献74.
75.
76.
77.
Nerea Rebolleda Ignacio Losada-Fernandez Gema Perez-Chacon Raquel Castejon Silvia Rosado Marta Morado Maria Teresa Vallejo-Cremades Andrea Martinez Juan A. Vargas-Nu?ez Paloma Perez-Aciego 《PloS one》2016,11(4)
B-cell chronic lymphocytic leukemia (CLL) remains an incurable disease, and despite the improvement achieved by therapeutic regimes developed over the last years still a subset of patients face a rather poor prognosis and will eventually relapse and become refractory to therapy. The natural rotenoid deguelin has been shown to induce apoptosis in several cancer cells and cell lines, including primary human CLL cells, and to act as a chemopreventive agent in animal models of induced carcinogenesis. In this work, we show that deguelin induces apoptosis in vitro in primary human CLL cells and in CLL-like cells from the New Zealand Black (NZB) mouse strain. In both of them, deguelin dowregulates AKT, NFκB and several downstream antiapoptotic proteins (XIAP, cIAP, BCL2, BCL-XL and survivin), activating the mitochondrial pathway of apoptosis. Moreover, deguelin inhibits stromal cell-mediated c-Myc upregulation and resistance to fludarabine, increasing fludarabine induced DNA damage. We further show that deguelin has activity in vivo against NZB CLL-like cells in an experimental model of CLL in young NZB mice transplanted with spleen cells from aged NZB mice with lymphoproliferation. Moreover, the combination of deguelin and fludarabine in this model prolonged the survival of transplanted mice at doses of both compounds that were ineffective when administered individually. These results suggest deguelin could have potential for the treatment of human CLL. 相似文献
78.
Background
Many new clinical prediction rules are derived and validated. But the design and reporting quality of clinical prediction research has been less than optimal. We aimed to assess whether design characteristics of validation studies were associated with the overestimation of clinical prediction rules’ performance. We also aimed to evaluate whether validation studies clearly reported important methodological characteristics.Methods
Electronic databases were searched for systematic reviews of clinical prediction rule studies published between 2006 and 2010. Data were extracted from the eligible validation studies included in the systematic reviews. A meta-analytic meta-epidemiological approach was used to assess the influence of design characteristics on predictive performance. From each validation study, it was assessed whether 7 design and 7 reporting characteristics were properly described.Results
A total of 287 validation studies of clinical prediction rule were collected from 15 systematic reviews (31 meta-analyses). Validation studies using case-control design produced a summary diagnostic odds ratio (DOR) 2.2 times (95% CI: 1.2–4.3) larger than validation studies using cohort design and unclear design. When differential verification was used, the summary DOR was overestimated by twofold (95% CI: 1.2 -3.1) compared to complete, partial and unclear verification. The summary RDOR of validation studies with inadequate sample size was 1.9 (95% CI: 1.2 -3.1) compared to studies with adequate sample size. Study site, reliability, and clinical prediction rule was adequately described in 10.1%, 9.4%, and 7.0% of validation studies respectively.Conclusion
Validation studies with design shortcomings may overestimate the performance of clinical prediction rules. The quality of reporting among studies validating clinical prediction rules needs to be improved. 相似文献79.
Patterns of population structure at microsatellite and mitochondrial DNA markers in the franciscana dolphin (Pontoporia blainvillei)
下载免费PDF全文
![点击此处可从《Ecology and evolution》网站下载免费的PDF全文](/ch/ext_images/free.gif)
María Constanza Gariboldi Juan Ignacio Túnez Mauricio Failla Marta Hevia María Victoria Panebianco María Natalia Paso Viola Alfredo Daniel Vitullo Humberto Luis Cappozzo 《Ecology and evolution》2016,6(24):8764-8776
The franciscana dolphin, Pontorporia blainvillei, is an endemic cetacean of the Atlantic coast of South America. Its coastal distribution and restricted movement patterns make this species vulnerable to anthropogenic factors, particularly to incidental bycatch. We used mitochondrial DNA control region sequences, 10 microsatellites, and sex data to investigate the population structure of the franciscana dolphin from a previously established management area, which includes the southern edge of its geographic range. F‐statistics and Bayesian cluster analyses revealed the existence of three genetically distinct populations. Based on the microsatellite loci, similar levels of genetic variability were found in the area; 13 private alleles were found in Monte Hermoso, but none in Claromecó. When considering the mitochondrial DNA control region sequences, lower levels of genetic diversity were found in Monte Hermoso, when compared to the other localities. Low levels of gene flow were found between most localities. Additionally, no evidence of isolation by distance nor sex‐biased dispersal was detected in the study area. In view of these results showing that populations from Necochea/Claromecó, Monte Hermoso, and Río Negro were found to be genetically distinct and the available genetic information for the species previously published, Argentina would comprise five distinct populations: Samborombón West/Samborombón South, Cabo San Antonio/Buenos Aires East, Necochea/Claromecó/Buenos Aires Southwest, Monte Hermoso, and Río Negro. In order to ensure the long‐term survival of the franciscana dolphin, management and conservation strategies should be developed considering each of these populations as different management units. 相似文献
80.