全文获取类型
收费全文 | 5748篇 |
免费 | 468篇 |
出版年
2023年 | 18篇 |
2022年 | 39篇 |
2021年 | 102篇 |
2020年 | 59篇 |
2019年 | 84篇 |
2018年 | 94篇 |
2017年 | 104篇 |
2016年 | 124篇 |
2015年 | 243篇 |
2014年 | 270篇 |
2013年 | 396篇 |
2012年 | 466篇 |
2011年 | 454篇 |
2010年 | 323篇 |
2009年 | 273篇 |
2008年 | 388篇 |
2007年 | 396篇 |
2006年 | 371篇 |
2005年 | 326篇 |
2004年 | 319篇 |
2003年 | 279篇 |
2002年 | 279篇 |
2001年 | 67篇 |
2000年 | 61篇 |
1999年 | 62篇 |
1998年 | 68篇 |
1997年 | 48篇 |
1996年 | 37篇 |
1995年 | 34篇 |
1994年 | 26篇 |
1993年 | 22篇 |
1992年 | 37篇 |
1991年 | 22篇 |
1990年 | 29篇 |
1989年 | 22篇 |
1988年 | 30篇 |
1987年 | 17篇 |
1986年 | 15篇 |
1985年 | 18篇 |
1984年 | 16篇 |
1983年 | 12篇 |
1982年 | 13篇 |
1981年 | 11篇 |
1979年 | 10篇 |
1978年 | 13篇 |
1977年 | 11篇 |
1975年 | 10篇 |
1974年 | 10篇 |
1973年 | 12篇 |
1966年 | 9篇 |
排序方式: 共有6216条查询结果,搜索用时 31 毫秒
911.
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
912.
913.
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
914.
915.
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
916.
Ok‐Ryul Song Christophe J Queval Raffaella Iantomasi Vincent Delorme Sabrina Marion Romain Veyron‐Churlet Elisabeth Werkmeister Michka Popoff Isabelle Ricard Samuel Jouny Nathalie Deboosere Frank Lafont Alain Baulard Laurent Marsollier Eik Hoffmann Priscille Brodin 《EMBO reports》2018,19(1):29-42
The interaction of Mycobacterium tuberculosis (Mtb) with pulmonary epithelial cells is critical for early stages of bacillus colonization and during the progression of tuberculosis. Entry of Mtb into epithelial cells has been shown to depend on F‐actin polymerization, though the molecular mechanisms are still unclear. Here, we demonstrate that mycobacterial uptake into epithelial cells requires rearrangements of the actin cytoskeleton, which are regulated by ADP‐ribosylation factor 1 (Arf1) and phospholipase D1 (PLD1), and is dependent on the M3 muscarinic receptor (M3R). We show that this pathway is controlled by Arf GTPase‐activating protein 1 (ArfGAP1), as its silencing has an impact on actin cytoskeleton reorganization leading to uncontrolled uptake and replication of Mtb. Furthermore, we provide evidence that this pathway is critical for mycobacterial entry, while the cellular infection with other pathogens, such as Shigella flexneri and Yersinia pseudotuberculosis, is not affected. Altogether, these results reveal how cortical actin plays the role of a barrier to prevent mycobacterial entry into epithelial cells and indicate a novel role for ArfGAP1 as a restriction factor of host–pathogen interactions. 相似文献
917.
Proteomics analysis of Medicago truncatula response to infection by the phytopathogenic bacterium Ralstonia solanacearum points to jasmonate and salicylate defence pathways
下载免费PDF全文
![点击此处可从《Cellular microbiology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
918.
919.
Guy Tran Van Nhieu Geneviève Dupont Laurent Combettes 《Biochimica et Biophysica Acta (BBA)/Molecular Cell Research》2018,1865(11):1838-1845
Recent reports have highlighted the pivotal role of Ca2+ during host cell infection by bacterial pathogens. Here, we review how bacterial pore-forming toxins (PFTs) trigger global Ca2+ signals to regulate cell adhesion-, inflammatory- or death processes. We comment recent reports describing the role of bacterial effectors injected by a type III secretion system (T3SS) as well as host cell players in the formation of Ca2+ microdomains during Shigella invasion and Chlamydia extrusion of host cells. We discuss how modeling and comparison between bacterial-induced and physiological Ca2+ microdomains provides insight into the critical parameters shaping the duration of local Ca2+ responses. 相似文献
920.
Matthieu Réfrégiers A. Laigle Béatrice Jollès Gavin V. Wheeler Laurent Chinsky 《European biophysics journal : EBJ》1997,26(3):277-281
An oligodeoxynucleotide has been synthesized, which mimics an ``antigene' oligonucleotide with a polypyrimidic stretch on
its 5′ side and is protected on its 3′ side against nucelases by a naturally forming and very stable hairpin, 5′GCGAAGC3′.
The in vitro degradation of the resulting oligonucleotide d(5′TTCTCGCGAAGC3′) has already been studied by fluorescence resonance
energy transfer (FRET) (Réfrégiers et al. 1996, J Biomol Struct Dyn 14: 365 – 371). The technique required the grafting of
fluorophores at both ends of the oligonucleotide. In the present work we have compared the hairpin formed in the presence
and in the absence of such fluorophores. This was achieved by the study of the Raman spectra (excitation at 257 nm) of the
oligodeoxynucleotides H, which forms the hairpin (5′TTCTCGCGAAGC3′), and a con-trol C (5′TTCTCCGGAAGC3′) which is unable to
form the hairpin. Resonance Raman spectroscopy with 257 nm excitation greatly favors the resonance of purines and therefore
the study of the 3′ part of the oligonucleotides. The difference spectrum obtained from resonance Raman spectra of C and H
showed marker peaks specific for hairpin formation. The search for these marker peaks in difference spectra involving the
Raman spectrum of H labeled by fluorophores and either C or H proved that the fluorophores do not modify the structure of
the hairpin but only the vibrations of the two terminal bases on which the fluorophores are grafted. The use of such labeling
is then justified in order to allow oligonucleotides protected by a hairpin on their 3′ side to be studied by fluorescence
spectroscopy.
Received: 13 December 1996 / Accepted: 7 April 1997 相似文献