全文获取类型
收费全文 | 2053篇 |
免费 | 180篇 |
国内免费 | 2篇 |
出版年
2023年 | 12篇 |
2022年 | 10篇 |
2021年 | 58篇 |
2020年 | 25篇 |
2019年 | 30篇 |
2018年 | 47篇 |
2017年 | 32篇 |
2016年 | 71篇 |
2015年 | 110篇 |
2014年 | 99篇 |
2013年 | 127篇 |
2012年 | 182篇 |
2011年 | 169篇 |
2010年 | 114篇 |
2009年 | 86篇 |
2008年 | 127篇 |
2007年 | 130篇 |
2006年 | 133篇 |
2005年 | 97篇 |
2004年 | 100篇 |
2003年 | 87篇 |
2002年 | 82篇 |
2001年 | 24篇 |
2000年 | 23篇 |
1999年 | 22篇 |
1998年 | 19篇 |
1997年 | 7篇 |
1996年 | 11篇 |
1995年 | 9篇 |
1994年 | 15篇 |
1993年 | 11篇 |
1992年 | 15篇 |
1991年 | 12篇 |
1990年 | 15篇 |
1989年 | 10篇 |
1988年 | 18篇 |
1987年 | 9篇 |
1986年 | 5篇 |
1985年 | 8篇 |
1984年 | 6篇 |
1983年 | 6篇 |
1982年 | 4篇 |
1980年 | 3篇 |
1979年 | 4篇 |
1978年 | 13篇 |
1977年 | 3篇 |
1975年 | 5篇 |
1974年 | 7篇 |
1973年 | 5篇 |
1967年 | 3篇 |
排序方式: 共有2235条查询结果,搜索用时 187 毫秒
991.
992.
Paul J. CaraDonna Laura A. Burkle Benjamin Schwarz Julian Resasco Tiffany M. Knight Gita Benadi Nico Blüthgen Carsten F. Dormann Qiang Fang Jochen Fründ Benoit Gauzens Christopher N. Kaiser‐Bunbury Rachael Winfree Diego P. Vzquez 《Ecology letters》2021,24(1):149-161
Most studies of plant–animal mutualistic networks have come from a temporally static perspective. This approach has revealed general patterns in network structure, but limits our ability to understand the ecological and evolutionary processes that shape these networks and to predict the consequences of natural and human‐driven disturbance on species interactions. We review the growing literature on temporal dynamics of plant–animal mutualistic networks including pollination, seed dispersal and ant defence mutualisms. We then discuss potential mechanisms underlying such variation in interactions, ranging from behavioural and physiological processes at the finest temporal scales to ecological and evolutionary processes at the broadest. We find that at the finest temporal scales (days, weeks, months) mutualistic interactions are highly dynamic, with considerable variation in network structure. At intermediate scales (years, decades), networks still exhibit high levels of temporal variation, but such variation appears to influence network properties only weakly. At the broadest temporal scales (many decades, centuries and beyond), continued shifts in interactions appear to reshape network structure, leading to dramatic community changes, including loss of species and function. Our review highlights the importance of considering the temporal dimension for understanding the ecology and evolution of complex webs of mutualistic interactions. 相似文献
993.
994.
995.
Gerard Wong Janine M. Trevillyan Benoit Fatou Michelle Cinel Jacquelyn M. Weir Jennifer F. Hoy Peter J. Meikle 《PloS one》2014,9(4)
Background
The increased risk of coronary artery disease in human immunodeficiency virus (HIV) positive patients is collectively contributed to by the human immunodeficiency virus and antiretroviral-associated dyslipidaemia. In this study, we investigate the characterisation of the plasma lipid profiles of treated HIV patients and the relationship of 316 plasma lipid species across multiple lipid classes with the risk of future cardiovascular events in HIV- positive patients.Methods
In a retrospective case-control study, we analysed plasma lipid profiles of 113 subjects. Cases (n = 23) were HIV-positive individuals with a stored blood sample available 12 months prior to their diagnosis of coronary artery disease (CAD). They were age and sex matched to HIV-positive individuals without a diagnosis of CAD (n = 45) and with healthy HIV-negative volunteers (n = 45).Results
Association of plasma lipid species and classes with HIV infection and cardiovascular risk in HIV were determined. In multiple logistic regression, we identified 83 lipids species and 7 lipid classes significantly associated with HIV infection and a further identified 74 lipid species and 8 lipid classes significantly associated with future cardiovascular events in HIV-positive subjects. Risk prediction models incorporating lipid species attained an area under the receiver operator characteristic curve (AUC) of 0.78 (0.775, 0.785)) and outperformed all other tested markers and risk scores in the identification of HIV-positive subjects with increased risk of cardiovascular events.Conclusions
Our results demonstrate that HIV-positive patients have significant differences in their plasma lipid profiles compared with healthy HIV-negative controls and that numerous lipid species were significantly associated with elevated cardiovascular risk. This suggests a potential novel application for plasma lipids in cardiovascular risk screening of HIV-positive patients. 相似文献996.
Ludovic Maertens Charlotte Erpicum Benoit Detry Silvia Blacher Bénédicte Lenoir Oriane Carnet Christel Péqueux Didier Cataldo Julie Lecomte Jenny Paupert Agnès Noel 《PloS one》2014,9(9)
It is now well accepted that multipotent Bone-Marrow Mesenchymal Stem Cells (BM-MSC) contribute to cancer progression through several mechanisms including angiogenesis. However, their involvement during the lymphangiogenic process is poorly described. Using BM-MSC isolated from mice of two different backgrounds, we demonstrate a paracrine lymphangiogenic action of BM-MSC both in vivo and in vitro. Co-injection of BM-MSC and tumor cells in mice increased the in vivo tumor growth and intratumoral lymphatic vessel density. In addition, BM-MSC or their conditioned medium stimulated the recruitment of lymphatic vessels in vivo in an ear sponge assay, and ex vivo in the lymphatic ring assay (LRA). In vitro, MSC conditioned medium also increased the proliferation rate and the migration of both primary lymphatic endothelial cells (LEC) and an immortalized lymphatic endothelial cell line. Mechanistically, these pro-lymphangiogenic effects relied on the secretion of Vascular Endothelial Growth Factor (VEGF)-A by BM-MSC that activates VEGF Receptor (VEGFR)-2 pathway on LEC. Indeed, the trapping of VEGF-A in MSC conditioned medium by soluble VEGF Receptors (sVEGFR)-1, -2 or the inhibition of VEGFR-2 activity by a specific inhibitor (ZM 323881) both decreased LEC proliferation, migration and the phosphorylation of their main downstream target ERK1/2. This study provides direct unprecedented evidence for a paracrine lymphangiogenic action of BM-MSC via the production of VEGF-A which acts on LEC VEGFR-2. 相似文献
997.
Roscoe Klinck Angélique Fourrier Philippe Thibault Johanne Toutant Mathieu Durand Elvy Lapointe Marie-Laure Caillet-Boudin Nicolas Sergeant Geneviève Gourdon Giovanni Meola Denis Furling Jack Puymirat Benoit Chabot 《PloS one》2014,9(9)
With the goal of identifying splicing alterations in myotonic dystrophy 1 (DM1) tissues that may yield insights into targets or mechanisms, we have surveyed mis-splicing events in three systems using a RT-PCR screening and validation platform. First, a transgenic mouse model expressing CUG-repeats identified splicing alterations shared with other mouse models of DM1. Second, using cell cultures from human embryonic muscle, we noted that DM1-associated splicing alterations were significantly enriched in cytoskeleton (e.g. SORBS1, TACC2, TTN, ACTN1 and DMD) and channel (e.g. KCND3 and TRPM4) genes. Third, of the splicing alterations occurring in adult DM1 tissues, one produced a dominant negative variant of the splicing regulator RBFOX1. Notably, half of the splicing events controlled by MBNL1 were co-regulated by RBFOX1, and several events in this category were mis-spliced in DM1 tissues. Our results suggest that reduced RBFOX1 activity in DM1 tissues may amplify several of the splicing alterations caused by the deficiency in MBNL1. 相似文献
998.
Fanny Morice‐Picard Eulalie Lasseaux Dorothée Cailley Audrey Gros Jérome Toutain Claudio Plaisant Delphine Simon Stéphane François Brigitte Gilbert‐Dussardier Josseline Kaplan Caroline Rooryck Didier Lacombe Benoit Arveiler 《Pigment cell & melanoma research》2014,27(1):59-71
Oculocutaneous albinism (OCA) is caused by mutations in six different genes, and their molecular diagnosis encompasses the search for point mutations and intragenic rearrangements. Here, we used high‐resolution array‐comparative genome hybridization (CGH) to search for rearrangements across exons, introns and regulatory sequences of four OCA genes: TYR, OCA2, TYRP1, and SLC45A2. We identified a total of ten new deletions in TYR, OCA2, and SLC45A2. A complex rearrangement of OCA2 was found in two unrelated patients. Whole‐genome sequencing showed deletion of a 184‐kb fragment (identical to a deletion previously found in Polish patients), whereby a large portion of the deleted sequence was re‐inserted after severe reshuffling into intron 1 of OCA2. The high‐resolution array‐CGH presented here is a powerful tool to detect gene rearrangements. Finally, we review all known deletions of the OCA1–4 genes reported so far in the literature and show that deletions or duplications account for 5.6% of all mutations identified in the OCA1–4 genes. 相似文献
999.
Agnes Cibiel Nam Nguyen Quang Karine Gombert Benoit Thézé Anikitos Garofalakis Frédéric Ducongé 《PloS one》2014,9(1)
Background
Cell-SELEX is now widely used for the selection of aptamers against cell surface biomarkers. However, despite negative selection steps using mock cells, this method sometimes results in aptamers against undesirable targets that are expressed both on mock and targeted cells. Studying these junk aptamers might be useful for further applications than those originally envisaged.Methodology/Principal Findings
Cell-SELEX was performed to identify aptamers against CHO-K1 cells expressing human Endothelin type B receptor (ETBR). CHO-K1 cells were used for negative selection of aptamers. Several aptamers were identified but no one could discriminate between both cell lines. We decided to study one of these aptamers, named ACE4, and we identified that it binds to the Annexin A2, a protein overexpressed in many cancers. Radioactive binding assays and flow cytometry demonstrated that the aptamer was able to bind several cancer cell lines from different origins, particularly the MCF-7 cells. Fluorescence microscopy revealed it could be completely internalized in cells in 2 hours. Finally, the tumor targeting of the aptamer was evaluated in vivo in nude mice xenograft with MCF-7 cells using fluorescence diffuse optical tomography (fDOT) imaging. Three hours after intravenous injection, the aptamer demonstrated a significantly higher uptake in the tumor compared to a scramble sequence.Conclusions/Significance
Although aptamers could be selected during cell-SELEX against other targets than those initially intended, they represent a potential source of ligands for basic research, diagnoses and therapy. Here, studying such aptamers, we identify one with high affinity for Annexin A2 that could be a promising tool for biomedical application. 相似文献1000.