全文获取类型
收费全文 | 3570篇 |
免费 | 310篇 |
国内免费 | 2篇 |
出版年
2023年 | 17篇 |
2022年 | 27篇 |
2021年 | 62篇 |
2020年 | 33篇 |
2019年 | 51篇 |
2018年 | 93篇 |
2017年 | 79篇 |
2016年 | 104篇 |
2015年 | 170篇 |
2014年 | 210篇 |
2013年 | 271篇 |
2012年 | 305篇 |
2011年 | 262篇 |
2010年 | 174篇 |
2009年 | 162篇 |
2008年 | 227篇 |
2007年 | 209篇 |
2006年 | 220篇 |
2005年 | 199篇 |
2004年 | 205篇 |
2003年 | 192篇 |
2002年 | 176篇 |
2001年 | 40篇 |
2000年 | 26篇 |
1999年 | 36篇 |
1998年 | 39篇 |
1997年 | 26篇 |
1996年 | 31篇 |
1995年 | 32篇 |
1994年 | 21篇 |
1993年 | 22篇 |
1992年 | 12篇 |
1991年 | 14篇 |
1990年 | 14篇 |
1989年 | 21篇 |
1988年 | 12篇 |
1987年 | 6篇 |
1986年 | 6篇 |
1985年 | 5篇 |
1984年 | 5篇 |
1983年 | 6篇 |
1982年 | 9篇 |
1981年 | 6篇 |
1980年 | 8篇 |
1979年 | 4篇 |
1978年 | 8篇 |
1977年 | 3篇 |
1976年 | 4篇 |
1974年 | 3篇 |
1960年 | 3篇 |
排序方式: 共有3882条查询结果,搜索用时 15 毫秒
91.
An increasing number of researchers are using the Saccharomyces cerevisiae chronological aging model to gain insight into the post-mitotic cellular aging. Recently, an alternative approach to the traditional cellular viability assay by colony-forming unit (CFU) counts, based on the propidium iodide (PI) staining combined with flow cytometry (PI-FCM), was proposed for the assessment of yeast chronological aging. Since the chronological aging assessment shows variations particularly concerning the aging media, in this work, the influence of the most common aging media (exhausted media or water) on the assessment of chronological aging by PI staining was studied. Our results show that this methodology is highly affected by the aging media. Indeed, a correlation between CFU counts and the percentage of PI-stained cells is only achieved with the exhausted media. As such, the assessment of yeast chronological aging by PI-FCM water should not be used. 相似文献
92.
Tom Pinceel Bram Vanschoenwinkel Aline Waterkeyn Maarten P. M. Vanhove Adrian Pinder Brian V. Timms Luc Brendonck 《Hydrobiologia》2013,700(1):313-327
Australia, and especially South-Western Australia, is a diversity hotspot for large branchiopod crustaceans. A significant proportion of this diversity is found in the anostracans (Crustacea, Anostraca) and particularly in the diverse genus Branchinella with at least 34 species. Members of this genus are found exclusively in temporary aquatic habitats which are increasingly threatened by secondary salinization and other anthropogenic pressures. The development of adequate conservation strategies is therefore considered a priority. To define conservation units, however, thorough knowledge of the taxonomy and phylogenetic position of extant lineages is essential. We reconstructed a large scale phylogeny of the Australian Branchinella by analyzing the 16S mitochondrial gene of 31 presumed species, complemented with analysis of morphological structures holding taxonomic information. Results revealed the presence of at least three new cryptic species. On the other hand, some Branchinella lineages, surviving in environments subjected to contrasting selection regimes, appeared to be conspecific. This suggests substantial physiological plasticity or important adaptive variation present in some species, potentially enabling them to better cope with environmental change, such as secondary salinization. Overall, these results further illustrate the benefits of combining molecular markers and classic morphological taxonomy and phylogeny to assess biodiversity and define conservation units in cryptic groups. 相似文献
93.
Luc Demange Fatma Nait Abdellah Olivier Lozach Yoan Ferandin Nohad Gresh Laurent Meijer Hervé Galons 《Bioorganic & medicinal chemistry letters》2013,23(1):125-131
Cyclin dependent kinase 5 (CDK5) is a serine/threonine kinase belonging to the cyclin dependent kinase (CDK) family. CDK5 is involved in numerous neuronal diseases (including Alzheimer’s or Parkinson’s diseases, stroke, traumatic brain injury), pain signaling and cell migration. In the present Letter, we describe syntheses and biological evaluations of new 2,6,9-trisubstituted purines, structurally related to roscovitine, a promising CDK inhibitor currently in clinical trials (CDK1/Cyclin B, IC50 = 350 nM; CDK5/p25, IC50 = 200 nM). These new molecules were synthesized using an original Buchwald–Hartwig catalytic procedure; several compounds (3j, 3k, 3l, 3e, 4k, 6b, 6c) displayed potent kinase inhibitory potencies against CDK5 (IC50 values ranging from 17 to 50 nM) and showed significant cell death inducing activities (IC50 values ranging from 2 to 9 μM on SH-SY5Y). The docking of the inhibitors into the ATP binding domain of the CDK5 catalytic site highlighted the discriminatory effect of a hydrogen bond involving the CDK5 Lys-89. In addition, the calculated final energy balances for complexation measured for several inhibitors is consistent with the ranking of the IC50 values. Lastly, we observed that several compounds exhibit submicromolar activities against DYRK1A (dual specificity, tyrosine phosphorylation regulated kinase 1A), a kinase involved in Down syndrome and Alzheimer’s disease (3g, 3h, 4m; IC50 values ranging from 300 to 400 nM). 相似文献
94.
Food security versus biodiversity protection: an example of land-sharing from East Africa 总被引:1,自引:0,他引:1
Jan Christian Habel Wolfgang W. Weisser Hilde Eggermont Luc Lens 《Biodiversity and Conservation》2013,22(6-7):1553-1555
The recent controversial debate on land-sharing versus land-sparing is clearly exemplified in the East African mountains, one of the most diverse biodiversity hotspots on our planet. In these areas, species richness is particularly concentrated in the mountain cloud forests which are surrounded by a sea of dry lowland savannas heavily encroached on by local communities. Sustainable land use practices in the lowlands, however, are necessary to safeguard the natural capital at higher elevations. The interdependence between sustainable land-use and conservation of biodiversity hotspots was underlined during a workshop held in the rural areas of Kenya, East Africa, early spring 2013. It was concluded that close links between livelihoods, natural capital and poverty remains a fundamental challenge in East Africa’s forest conservation efforts. 相似文献
95.
Arturo Roca-Rivada Cecilia Castelao Lucía L. Senin María O. Landrove Javier Baltar Ana Belén Crujeiras Luisa María Seoane Felipe F. Casanueva María Pardo 《PloS one》2013,8(4)
Exercise provides clear beneficial effects for the prevention of numerous diseases. However, many of the molecular events responsible for the curative and protective role of exercise remain elusive. The recent discovery of FNDC5/irisin protein that is liberated by muscle tissue in response to exercise might be an important finding with regard to this unsolved mechanism. The most striking aspect of this myokine is its alleged capacity to drive brown-fat development of white fat and thermogenesis. However, the nature and secretion form of this new protein is controversial. The present study reveals that rat skeletal muscle secretes a 25 kDa form of FNDC5, while the 12 kDa/irisin theoretical peptide was not detected. More importantly, this study is the first to reveal that white adipose tissue (WAT) also secretes FNDC5; hence, it may also behave as an adipokine. Our data using rat adipose tissue explants secretomes proves that visceral adipose tissue (VAT), and especially subcutaneous adipose tissue (SAT), express and secrete FNDC5. We also show that short-term periods of endurance exercise training induced FNDC5 secretion by SAT and VAT. Moreover, we observed that WAT significantly reduced FNDC5 secretion in fasting animals. Interestingly, WAT of obese animals over-secreted this hormone, which might suggest a type of resistance. Because 72% of circulating FNDC5/irisin was previously attributed to muscle secretion, our findings suggest a muscle-adipose tissue crosstalk through a regulatory feedback mechanism. 相似文献
96.
Sophie Pinel Jihane Mriouah Marc Vandamme Alicia Chateau Fran?ois Plénat Eric Guérin Luc Taillandier Valérie Bernier-Chastagner Jean-Louis Merlin Pascal Chastagner 《PloS one》2013,8(7)
In high-grade gliomas, the identification of patients that could benefit from EGFR inhibitors remains a challenge, hindering the use of these agents. Using xenografts models, we evaluated the antitumor effect of the combined treatment “gefitinib + radiotherapy” and aimed to identify the profile of responsive tumors. Expression of phosphorylated proteins involved in the EGFR-dependent signaling pathways was analyzed in 10 glioma models. We focused on three models of anaplastic oligodendrogliomas (TCG2, TCG3 and TCG4) harboring high levels of phospho-EGFR, phospho-AKT and phospho-MEK1. They were treated with gefitinib (GEF 75 mg/kg/day x 5 days/week, for 2 weeks) and/or fractionated radiotherapy (RT: 5x2Gy/week for 2 weeks). Our results showed that GEF and/or RT induced significant tumor growth delays. However, only the TCG3 xenografts were highly responsive to the combination GEF+RT, with ∼50% of tumor cure. Phosphoproteins analysis five days after treatment onset demonstrated in TCG3 xenografts, but not in TCG2 model, that the EGFR-dependent pathways were inhibited after GEF treatment. Moreover, TCG3-bearing mice receiving GEF monotherapy exhibited a transient beneficial therapeutic response, rapidly followed by tumor regrowth, along with a major vascular remodeling. Taken together, our data evoked an “EGFR-addictive” behavior for TCG3 tumors. This study confirms that combination of gefitinib with fractionated irradiation could be a potent therapeutic strategy for anaplastic oligodendrogliomas harboring EGFR abnormalities but this treatment seems mainly beneficial for “EGFR-addictive” tumors. Unfortunately, neither the usual molecular markers (EGFR amplification, PTEN loss) nor the basal overexpression of phosphoproteins were useful to distinguish this responsive tumor. Evaluating the impact of TKIs on the EGFR-dependent pathways during the treatment might be more relevant, and requires further validation. 相似文献
97.
98.
Balancing competition for resources with multiple pest regulation in diversified agroecosystems: a process‐based approach to reconcile diversification and productivity
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)
Charlotte Poeydebat Dominique Carval Luc de Lapeyre de Bellaire Philippe Tixier 《Ecology and evolution》2016,6(23):8607-8616
Agroecosystem plant diversification can enhance pest biological regulation and is a promising alternative to pesticide application. However, the costs of competition for resources between plants may exceed the benefits gained by pest regulation. To disentangle the interactions between pest regulation and competition, we developed a generic process‐based approach that accounts for the effects of an associated plant and leaf and root pests on biomass production. We considered three crop–plant associations that differ in competition profiles, and we simulated biomass production under wide ranges of both pest regulation rates and resources’ availability. We analyzed outputs to quantify the pest regulation service level that would be required to attain monoculture yield and other production goals. Results showed that pest regulation requirements were highly dependent on the profile of resource interception of the associated plant and on resources’ availability. Pest regulation and the magnitude of competition between plants interacted in determining the balance between nitrogen and radiation uptake by the crop. Our findings suggest that productivity of diversified agroecosystems relative to monoculture should be optimized by assembling plants whose characteristics balance crops’ resource acquisition. The theoretical insights from our study draw generic rules for vegetation assemblage to optimize trade‐offs between pest regulation and production. Our findings and approach may have implications in understanding, theorizing and implementing agroecosystem diversification. By its generic and adaptable structure, our approach should be useful for studying the effects of diversification in many agroecosystems. 相似文献
99.
100.
Luc Villandre David A. Stephens Aurelie Labbe Huldrych F. Günthard Roger Kouyos Tanja Stadler The Swiss HIV Cohort Study 《PloS one》2016,11(2)