全文获取类型
收费全文 | 6044篇 |
免费 | 491篇 |
出版年
2023年 | 20篇 |
2022年 | 49篇 |
2021年 | 111篇 |
2020年 | 68篇 |
2019年 | 93篇 |
2018年 | 99篇 |
2017年 | 113篇 |
2016年 | 133篇 |
2015年 | 252篇 |
2014年 | 280篇 |
2013年 | 417篇 |
2012年 | 480篇 |
2011年 | 474篇 |
2010年 | 330篇 |
2009年 | 279篇 |
2008年 | 402篇 |
2007年 | 406篇 |
2006年 | 381篇 |
2005年 | 334篇 |
2004年 | 325篇 |
2003年 | 288篇 |
2002年 | 293篇 |
2001年 | 73篇 |
2000年 | 68篇 |
1999年 | 67篇 |
1998年 | 73篇 |
1997年 | 54篇 |
1996年 | 43篇 |
1995年 | 40篇 |
1994年 | 31篇 |
1993年 | 27篇 |
1992年 | 47篇 |
1991年 | 26篇 |
1990年 | 31篇 |
1989年 | 29篇 |
1988年 | 35篇 |
1987年 | 19篇 |
1986年 | 17篇 |
1985年 | 21篇 |
1984年 | 20篇 |
1983年 | 13篇 |
1982年 | 15篇 |
1981年 | 12篇 |
1979年 | 12篇 |
1978年 | 14篇 |
1977年 | 11篇 |
1975年 | 10篇 |
1974年 | 11篇 |
1973年 | 12篇 |
1966年 | 8篇 |
排序方式: 共有6535条查询结果,搜索用时 15 毫秒
941.
942.
Mélanie Gaubert Marion Marlinge Marine Alessandrini Marc Laine Laurent Bonello Julien Fromonot Jennifer Cautela Franck Thuny Jeremie Barraud Giovanna Mottola Pascal Rossi Emmanuel Fenouillet Jean Ruf Régis Guieu Franck Paganelli 《Purinergic signalling》2018,14(2):191-199
The role of serum uric acid in coronary artery disease has been extensively investigated. It was suggested that serum uric acid level (SUA) is an independent predictor of endothelial dysfunction and related to coronary artery lesions. However, the relationship between SUA and severity of coronary atherosclerosis evaluated via endothelial dysfunction using peripheral arterial tone (PAT) and the reactive hyperhemia index (RHI) has not been investigated during a first episode of acute coronary syndrome (ACS). The aim of our study was to address this point. We prospectively enrolled 80 patients with a first episode of ACS in a single-center observational study. All patients underwent coronary angiography, evaluation of endothelial function via the RHI, and SUA measurement. The severity of the coronary artery lesion was assessed angiographically, and patients were classified in three groups based on the extent of disease and Gensini and SYNTAX scores. Endothelial function was considered abnormal if RHI?<?1.67. We identified a linear correlation between SUA and RHI (R2 =?0.66 P <?0.001). In multivariable analyses, SUA remained associated with RHI, even after adjustment for traditional cardiovascular risk factors and renal function. SUA was associated with severity of coronary artery disease. SUA is associated with severity of coronary atherosclerosis in patients with asymptomatic hyperuricemia. This inexpensive, readily measured biological parameter may be useful to monitor ACS patients. 相似文献
943.
Jean-François Fournier Yushma Bhurruth-Alcor Branislav Musicki Jérome Aubert Michèle Aurelly Claire Bouix-Peter Karinne Bouquet Laurent Chantalat Marion Delorme Bénédicte Drean Gwenaelle Duvert Nicolas Fleury-Bregeot Blanche Gauthier Karine Grisendi Craig S. Harris Laurent F. Hennequin Tatiana Isabet Florence Joly Loïc Tomas 《Bioorganic & medicinal chemistry letters》2018,28(17):2985-2992
A series of squaramide-based hydroxamic acids were designed, synthesized and evaluated against human HDAC enzyme. Squaramides were found to be potent in the Hut78 cell line, but initially suffered from low solubility. Leads with improved solubility and metabolic profiles were shown to be class I, IIB and IV selective. 相似文献
944.
Gilles Ouvry Franck Bihl Claire Bouix-Peter Olivier Christin Claire Defoin-Platel Sophie Deret Christophe Feret David Froude Feriel Hacini-Rachinel Craig S. Harris Catherine Hervouet Guillaume Lafitte Anne-Pascale Luzy Branislav Musicki Danielle Orfila Veronique Parnet Coralie Pascau Jonathan Pascau Laurent F. Hennequin 《Bioorganic & medicinal chemistry letters》2018,28(8):1269-1273
Progress in the identification of suitable RORγ inverse agonists as clinical candidates has been hampered by the high lipophilicity that seems required for high potency on this nuclear receptor. In this context, we decided to focus on the replacement of the hydroxymethyl group found on known modulators to determine if more polarity could be tolerated in this position. SAR of the replacement of this moiety is presented in this article leading to the identification of sulfoximine derivatives as potent modulators with pharmacological activity in the in vivo mouse Imiquimod psoriasis model. 相似文献
945.
Etienne Thoreau Jean-Marie Arlabosse Claire Bouix-Peter Sandrine Chambon Laurent Chantalat Sébastien Daver Laurence Dumais Gwenaëlle Duvert Angélique Feret Gilles Ouvry Jonathan Pascau Catherine Raffin Nicolas Rodeville Catherine Soulet Samuel Tabet Sandrine Talano Thibaud Portal 《Bioorganic & medicinal chemistry letters》2018,28(10):1736-1741
Retinoids have a dominant role in topical acne therapy and to date, only RARβ and RARγ dual agonists have reached the market. Given the tissue distribution of RAR isoforms, it was hypothesized that developing RARγ -selective agonists could yield a new generation of topical acne treatments that would increase safety margins while maintaining the robust efficacy of previous drugs. Structural knowledge derived from the X-ray structure of known γ-selective CD437, suggested the design of a novel triaryl series of agonists which was optimized and ultimately led to the discovery of Trifarotene/CD5789. 相似文献
946.
947.
Laurent Loison 《Biology & philosophy》2018,33(3-4):29
Since the 1990s, the terms “Lamarckism” and “Lamarckian” have seen a significant resurgence in biological publications. The discovery of new molecular mechanisms (DNA methylation, histone modifications, RNA interference, etc.) have been interpreted as evidence supporting the reality and efficiency of the inheritance of acquired characters, and thus the revival of Lamarckism. The present paper aims at giving a critical evaluation of such interpretations. I argue that two types of arguments allow to draw a clear distinction between the genuine Lamarckian concept of inheritance of acquired characters and transgenerational epigenetic inheritance. The first concerns the explanandum of the processes under consideration: molecular mechanisms of transgenerational epigenetic inheritance are understood as evolved products of natural selection. This means that the kind of inheritance of acquired characters they might be responsible for is an obligatory emergent feature of evolution, whereas traditional Lamarckisms conceived the inheritance of acquired characters as a property inherent in living matter itself. The second argument concerns the explanans of the inheritance of acquired characters: in light of current knowledge, epigenetic mechanisms are not able to drive adaptive evolution by themselves. Emergent Lamarckian phenomena would be possible if and only if individual epigenetic variation allowed the inheritance of acquired characters to be a factor of unlimited change. This implies specific requirements for epigenetic variation, which I explicitly define and expand upon. I then show that given current knowledge, these requirements are not empirically grounded. 相似文献
948.
949.
Rafika Brakni Monia Ali Ahmed Pauline Burger Aurélie Schwing Grégory Michel Christelle Pomares Lillia Hasseine Laurent Boyer Xavier Fernandez Anne Landreau Thomas Michel 《化学与生物多样性》2018,15(4)
Lichens are complex symbiotic organisms able to produce a vast array of compounds. The Algerian lichen diversity has only prompted little interest even given the 1085 species listed. Herein, the chemodiversity of four Algerian lichens including Cladonia rangiformis, Ramalina farinaceae, R. fastigiata, and Roccella phycopsis was investigated. A dereplication strategy, using ultra high performance liquid chromatography‐high resolution‐electrospray ionization‐mass spectrometry (UHPLC‐HRMS/MS), was carried out for a comprehensive characterization of their substances including phenolics, depsides, depsidones, depsones, dibenzofurans, and aliphatic acids. Some known compounds were identified for the first time in some species. Additionally, the lichenic extracts were evaluated for their antifungal and antimicrobial activities on human pathogenic strains (Candida albicans, C. glabrata, Aspergillus fumigatus, Staphylococcus aureus, and Escherichia coli). Cyclohexane extracts were found particularly active against human pathogenic fungi with MIC80 values ranging from 8 to 62.5 μg/mL, without cytotoxicity. This study highlights the therapeutic and prophylactic potential of lichenic extracts as antibacterial and antifungal agents. 相似文献
950.