全文获取类型
收费全文 | 4076篇 |
免费 | 304篇 |
国内免费 | 1篇 |
出版年
2024年 | 5篇 |
2023年 | 43篇 |
2022年 | 80篇 |
2021年 | 144篇 |
2020年 | 111篇 |
2019年 | 114篇 |
2018年 | 137篇 |
2017年 | 132篇 |
2016年 | 168篇 |
2015年 | 231篇 |
2014年 | 268篇 |
2013年 | 299篇 |
2012年 | 361篇 |
2011年 | 318篇 |
2010年 | 200篇 |
2009年 | 187篇 |
2008年 | 216篇 |
2007年 | 225篇 |
2006年 | 164篇 |
2005年 | 172篇 |
2004年 | 177篇 |
2003年 | 125篇 |
2002年 | 144篇 |
2001年 | 36篇 |
2000年 | 19篇 |
1999年 | 32篇 |
1998年 | 27篇 |
1997年 | 40篇 |
1996年 | 20篇 |
1995年 | 21篇 |
1994年 | 17篇 |
1993年 | 15篇 |
1992年 | 9篇 |
1991年 | 7篇 |
1990年 | 10篇 |
1989年 | 10篇 |
1988年 | 5篇 |
1987年 | 9篇 |
1985年 | 6篇 |
1984年 | 12篇 |
1983年 | 5篇 |
1982年 | 8篇 |
1981年 | 10篇 |
1980年 | 3篇 |
1979年 | 4篇 |
1977年 | 9篇 |
1976年 | 5篇 |
1975年 | 3篇 |
1974年 | 3篇 |
1961年 | 3篇 |
排序方式: 共有4381条查询结果,搜索用时 15 毫秒
51.
Hans Erik Bøtker Hector Alejandro Cabrera-Fuentes Marisol Ruiz-Meana Gerd Heusch Michel Ovize 《Journal of cellular and molecular medicine》2020,24(5):2717-2729
Pre-clinical studies have indicated that mitoprotective drugs may add cardioprotection beyond rapid revascularization, antiplatelet therapy and risk modification. We review the clinical efficacy of mitoprotective drugs that have progressed to clinical testing comprising cyclosporine A, KAI-9803, MTP131 and TRO 40303. Whereas cyclosporine may reduce infarct size in patients undergoing primary angioplasty as evaluated by release of myocardial ischaemic biomarkers and infarct size imaging, the other drugs were not capable of demonstrating this effect in the clinical setting. The absent effect leaves the role of the mitochondrial permeability transition pore for reperfusion injury in humans unanswered and indicates that targeting one single mechanism to provide mitoprotection may not be efficient. Moreover, the lack of effect may relate to favourable outcome with current optimal therapy, but conditions such as age, sex, diabetes, dyslipidaemia and concurrent medications may also alter mitochondrial function. However, as long as the molecular structure of the pore remains unknown and specific inhibitors of its opening are lacking, the mitochondrial permeability transition pore remains a target for alleviation of reperfusion injury. Nevertheless, taking conditions such as ageing, sex, comorbidities and co-medication into account may be of paramount importance during the design of pre-clinical and clinical studies testing mitoprotective drugs. 相似文献
52.
53.
Andrs García María Cecilia Scarf Alejandro Loydi Roberto Alejandro Distel 《Austral ecology》2020,45(1):70-78
In this study, we made an attempt to reveal how competition intensity from established plants impacts on palatable and unpalatable grass seedlings recruitment, in a natural mesic grassland of central Argentina. Our objective was to assess the seedling recruitment of a palatable species (Chascolytrum subaristatum) and an unpalatable species (Nassella trichotoma) in microsites differing in competition intensity from established plants. Identity (C. subaristatum and N. trichotoma) and defoliation severity were used as surrogate for competition intensity. In March 2017, we permanently marked established individuals of N. trichotoma and C. subaristatum and placed two circular plots adjacent to each individual. In one plot we added seeds of N. trichotoma and in the other seeds of C. subaristatum. After seeding, established plants were randomly assigned to one of three level of defoliation: without defoliation, low defoliation severity and high defoliation severity. From April to November 2017 (i.e. over a complete annual growing cycle), we measured seedling density, recruitment and growth. Our results supported the hypothesis that seedlings of palatable grasses are more competitive than seedlings of unpalatable grasses. Seedling of the palatable grass C. subaristatum recruited successfully regardless the intensity of competition from established plants, whereas seedlings of the unpalatable grass N. trichotoma recruited better under low competitive pressure from established plants. Our results suggest that the availability of microsites with low competitive pressure from the established vegetation, created by selective grazing of palatable grasses, promotes the recruitment of unpalatable grass seedlings. This mechanism may contribute to the species replacement process commonly observed in heavy grazed grasslands. 相似文献
54.
Sigrid van Grinsven Jaap S. Sinninghe Damsté Alejandro Abdala Asbun Julia C. Engelmann John Harrison Laura Villanueva 《Environmental microbiology》2020,22(2):766-782
Methanotrophic bacteria play a key role in limiting methane emissions from lakes. It is generally assumed that methanotrophic bacteria are mostly active at the oxic-anoxic transition zone in stratified lakes, where they use oxygen to oxidize methane. Here, we describe a methanotroph of the genera Methylobacter that is performing high-rate (up to 72 μM day−1) methane oxidation in the anoxic hypolimnion of the temperate Lacamas Lake (Washington, USA), stimulated by both nitrate and sulfate addition. Oxic and anoxic incubations both showed active methane oxidation by a Methylobacter species, with anoxic rates being threefold higher. In anoxic incubations, Methylobacter cell numbers increased almost two orders of magnitude within 3 days, suggesting that this specific Methylobacter species is a facultative anaerobe with a rapid response capability. Genomic analysis revealed adaptations to oxygen-limitation as well as pathways for mixed-acid fermentation and H2 production. The denitrification pathway was incomplete, lacking the genes narG/napA and nosZ, allowing only for methane oxidation coupled to nitrite-reduction. Our data suggest that Methylobacter can be an important driver of the conversion of methane in oxygen-limited lake systems and potentially use alternative electron acceptors or fermentation to remain active under oxygen-depleted conditions. 相似文献
55.
Jessica Voisin Francesca Farina Swati Naphade Morgane Fontaine Kizito‐Tshitoko Tshilenge Carlos Galicia Aguirre Alejandro Lopez‐Ramirez Julia Dancourt Aurélie Ginisty Satish Sasidharan Nair Kuruwitage Lakshika Madushani Ningzhe Zhang Fran?ois‐Xavier Lejeune Marc Verny Judith Campisi Lisa M. Ellerby Christian Neri 《Aging cell》2020,19(11)
56.
Fabiola Marín‐Aguilar Ana V. Lechuga‐Vieco Elísabet Alcocer‐Gmez Beatriz Castejn‐Vega Javier Lucas Carlos Garrido Alejandro Peralta‐Garcia Antonio J. Prez‐Pulido Alfonso Varela‐Lpez Jos L. Quiles Bernhard Ryffel Ignacio Flores Pedro Bulln Jesús Ruiz‐Cabello Mario D. Cordero 《Aging cell》2020,19(1)
While NLRP3‐inflammasome has been implicated in cardiovascular diseases, its role in physiological cardiac aging is largely unknown. During aging, many alterations occur in the organism, which are associated with progressive impairment of metabolic pathways related to insulin resistance, autophagy dysfunction, and inflammation. Here, we investigated the molecular mechanisms through which NLRP3 inhibition may attenuate cardiac aging. Ablation of NLRP3‐inflammasome protected mice from age‐related increased insulin sensitivity, reduced IGF‐1 and leptin/adiponectin ratio levels, and reduced cardiac damage with protection of the prolongation of the age‐dependent PR interval, which is associated with atrial fibrillation by cardiovascular aging and reduced telomere shortening. Furthermore, old NLRP3 KO mice showed an inhibition of the PI3K/AKT/mTOR pathway and autophagy improvement, compared with old wild mice and preserved Nampt‐mediated NAD+ levels with increased SIRT1 protein expression. These findings suggest that suppression of NLRP3 prevented many age‐associated changes in the heart, preserved cardiac function of aged mice and increased lifespan. 相似文献
57.
Gloria Gutirrez‐Venegas Manuel Alejandro Snchez‐Carballido Claire Delmas Surez Juan Arturo Gmez‐Mora Nomie Bonneau 《Cell biology international》2020,44(3):686-720
Squamous cell carcinoma (SCC) of the tongue is associated with tobacco use, alcohol abuse, and human papillomavirus (HPV) infections. While clinical outcomes have recently improved for HPV‐positive patients in general, 50% of patients suffering from tongue cancer die within 5 years of being diagnosed. Flavonoids are secondary plant metabolites with a wide range of biological activities including antioxidant, anti‐inflammatory, and anticancer activities. Flavonoids have generated high interest as therapeutic agents owing to their low toxicity and their effects on a large variety of cancer cell types. In this literature review, we evaluate the actions of flavonoids on SCC of the tongue demonstrated in both in vivo and in vitro models. 相似文献
58.
59.
Ann Carla Staver Paulo M. Brando Jos Barlow Douglas C. Morton C.E. Timothy Paine Yadvinder Malhi Alejandro Araujo Murakami Jhon del Aguila Pasquel 《Ecology letters》2020,23(1):99-106
Understory fires represent an accelerating threat to Amazonian tropical forests and can, during drought, affect larger areas than deforestation itself. These fires kill trees at rates varying from < 10 to c. 90% depending on fire intensity, forest disturbance history and tree functional traits. Here, we examine variation in bark thickness across the Amazon. Bark can protect trees from fires, but it is often assumed to be consistently thin across tropical forests. Here, we show that investment in bark varies, with thicker bark in dry forests and thinner in wetter forests. We also show that thinner bark translated into higher fire‐driven tree mortality in wetter forests, with between 0.67 and 5.86 gigatonnes CO2 lost in Amazon understory fires between 2001 and 2010. Trait‐enabled global vegetation models that explicitly include variation in bark thickness are likely to improve the predictions of fire effects on carbon cycling in tropical forests. 相似文献
60.
Alfredo Floristn Leah Morales Douglas Hanniford Carlos Martinez Elena Castellano‐Sanz Igor Dolgalev Alejandro Ulloa‐Morales Eleazar Vega‐Saenz de Miera Una Moran Farbod Darvishian Iman Osman Tomas Kirchhoff Eva Hernando 《Pigment cell & melanoma research》2020,33(3):466-479
Next‐generation sequencing has enabled genetic and genomic characterization of melanoma to an unprecedent depth. However, the high mutational background plus the limited depth of coverage of whole‐genome sequencing performed on cutaneous melanoma samples make the identification of novel driver mutations difficult. We sought to explore the somatic mutation portfolio in exonic and gene regulatory regions in human melanoma samples, for which we performed targeted sequencing of tumors and matched germline DNA samples from 89 melanoma patients, identifying known and novel recurrent mutations. Two recurrent mutations found in the RPS27 promoter associated with decreased RPS27 mRNA levels in vitro. Data mining and IHC analyses revealed a bimodal pattern of RPS27 expression in melanoma, with RPS27‐low patients displaying worse prognosis. In vitro characterization of RPS27‐high and RPS27‐low melanoma cell lines, as well as loss‐of‐function experiments, demonstrated that high RPS27 status provides increased proliferative and invasive capacities, while low RPS27 confers survival advantage in low attachment and resistance to therapy. Additionally, we demonstrate that 10 other cancer types harbor bimodal RPS27 expression, and in those, similarly to melanoma, RPS27‐low expression associates with worse clinical outcomes. RPS27 promoter mutation could thus represent a mechanism of gene expression modulation in melanoma patients, which may have prognostic and predictive implications. 相似文献