全文获取类型
收费全文 | 99篇 |
免费 | 2篇 |
出版年
2023年 | 1篇 |
2021年 | 4篇 |
2019年 | 1篇 |
2018年 | 4篇 |
2017年 | 3篇 |
2016年 | 5篇 |
2015年 | 5篇 |
2014年 | 2篇 |
2013年 | 5篇 |
2012年 | 4篇 |
2011年 | 5篇 |
2010年 | 2篇 |
2009年 | 4篇 |
2008年 | 9篇 |
2007年 | 5篇 |
2006年 | 6篇 |
2005年 | 8篇 |
2004年 | 5篇 |
2003年 | 1篇 |
2002年 | 2篇 |
2001年 | 1篇 |
2000年 | 3篇 |
1999年 | 1篇 |
1998年 | 1篇 |
1997年 | 2篇 |
1995年 | 1篇 |
1993年 | 1篇 |
1992年 | 1篇 |
1990年 | 2篇 |
1989年 | 2篇 |
1986年 | 1篇 |
1985年 | 2篇 |
1984年 | 1篇 |
1983年 | 1篇 |
排序方式: 共有101条查询结果,搜索用时 843 毫秒
91.
Annelise Tran Grégory L’Ambert Gilles Balança Sophie Pradier Vladimir Grosbois Thomas Balenghien Thierry Baldet Sylvie Lecollinet Agnès Leblond Nicolas Gaidet-Drapier 《EcoHealth》2017,14(3):474-489
West Nile disease, caused by the West Nile virus (WNV), is a mosquito-borne zoonotic disease affecting humans and horses that involves wild birds as amplifying hosts. The mechanisms of WNV transmission remain unclear in Europe where the occurrence of outbreaks has dramatically increased in recent years. We used a dataset on the competence, distribution, abundance, diversity and dispersal of wild bird hosts and mosquito vectors to test alternative hypotheses concerning the transmission of WNV in Southern France. We modelled the successive processes of introduction, amplification, dispersal and spillover of WNV to incidental hosts based on host–vector contact rates on various land cover types and over four seasons. We evaluated the relative importance of the mechanisms tested using two independent serological datasets of WNV antibodies collected in wild birds and horses. We found that the same transmission processes (seasonal virus introduction by migratory birds, Culex modestus mosquitoes as amplifying vectors, heterogeneity in avian host competence, absence of ‘dilution effect’) best explain the spatial variations in WNV seroprevalence in the two serological datasets. Our results provide new insights on the pathways of WNV introduction, amplification and spillover and the contribution of bird and mosquito species to WNV transmission in Southern France. 相似文献
92.
Calcineurin phosphatase and cyclophilin A are cellular components involved in fungal morphogenesis and virulence. Their roles were investigated in the phytopathogenic fungus Botrytis cinerea using gene inactivation, drug inhibition and cDNA macroarrays approaches. First, the BCP1 gene coding for cyclophilin A was identified and inactivated by homologous recombination. The bcp1Delta null mutant obtained was still able to develop infection structures but was altered in symptom development on bean and tomato leaves. Opposite to this, calcineurin inhibition using cyclosporin A (CsA) modified hyphal morphology and prevented infection structure formation. CsA drug pattern signature on macroarrays allowed the identification of 18 calcineurin-dependent (CND) genes among 2839 B. cinerea genes. Among the co-regulated CND genes, three were shown to be organized as a physical cluster that could be involved in secondary metabolism. The signature of BCP1 inactivation on macroarrays allowed the identification of only three BCP1 cyclophilin-dependent (CPD) genes that were different from CND genes. Finally, no CsA drug pattern signature was observed in the bcp1Delta null mutant which provided a molecular target validation of the drug. 相似文献
93.
Gu WJ Abbas N Lagunes MZ Parent A Pradier L Bohme GA Agid Y Hirsch EC Raisman-Vozari R Brice A 《Journal of neurochemistry》2000,74(4):1773-1776
The rat parkin cDNA sequence was characterized after screening a rat hypothalamus cDNA library with a 32P-labeled probe containing the entire open reading frame of the human parkin cDNA. This sequence encompasses 1,576 bp and contains a single open reading frame that encodes a 465-amino acid protein. The rat parkin amino acid sequence exhibits a very striking homology to the human and mouse parkin, with 85 and 95% identity, respectively. Both the N-terminal ubiquitin and the ring-IBR (in between ring)-ring finger domains appear to be highly conserved among rat, human, and mouse parkin. An affinity-purified polyclonal antibody (ASP5p) was generated with a synthetic peptide corresponding to amino acids 295-311 of the parkin sequence, which is identical in the three species. Western blotting revealed that ASP5p recognizes a single 52-kDa band, which corresponds to the molecular mass of the parkin protein. Immunostaining with ASP5p showed that parkin is principally located in the cytoplasm of neurons that are widely distributed in the rat brain. Parkin-immunoreactive neurons abound in structures that are specifically targeted in Parkinson's disease, e.g., subtantia nigra, but are also present in unaffected structures, e.g., cerebellum. Furthermore, parkin-enriched glial cells can be detected in various nuclei of the rat brain. Thus, the role of parkin may be much more global than previously thought on the basis of genetic findings gathered in cases of early-onset parkinsonism. 相似文献
94.
Lopez-Perez E Dumanchin C Czech C Campion D Goud B Pradier L Frebourg T Checler F 《Biochemical and biophysical research communications》2000,275(3):910-915
Presenilins 1 and 2 are two homologous proteins which, when mutated, appear responsible for most of the early-onset familial forms of Alzheimer's disease. Among various functional aspects, presenilins appear to behave as chaperoning partners of a series of proteins including the beta-amyloid precursor protein. Recently, presenilins were shown to interact with Rab11, a GTPase involved in intracellular transport. This suggested that Rab11-presenilin interaction could influence the routing of betaAPP and thereby modulate its maturation. In this context, we examined whether overexpression of Rab11 or its constitutively active mutant Rab11Q70L could affect betaAPP maturation in human HEK293 cells. We show here that the overexpression of both Rab11-related proteins does not modify the recovery of secreted sAPPalpha or Abeta in HEK293 cells expressing wild-type betaAPP or betaAPP harboring the Swedish double mutation. These data indicate that Rab11 does not influence betaAPP processing in HEK293 cells. However, it does not preclude the possibility for Rab11 to modulate other presenilin-mediated functions in human cells. 相似文献
95.
96.
Thomas Pradeu Bertrand Daignan-Fornier Andrew Ewald Pierre-Luc Germain Samir Okasha Anya Plutynski Sébastien Benzekry Marta Bertolaso Mina Bissell Joel S. Brown Benjamin Chin-Yee Ian Chin-Yee Hans Clevers Laurent Cognet Marie Darrason Emmanuel Farge Jean Feunteun Jérôme Galon Elodie Giroux Sara Green Fridolin Gross Fanny Jaulin Rob Knight Ezio Laconi Nicolas Larmonier Carlo Maley Alberto Mantovani Violaine Moreau Pierre Nassoy Elena Rondeau David Santamaria Catherine M. Sawai Andrei Seluanov Gregory D. Sepich-Poore Vanja Sisirak Eric Solary Sarah Yvonnet Lucie Laplane 《Biological reviews of the Cambridge Philosophical Society》2023,98(5):1668-1686
Cancers rely on multiple, heterogeneous processes at different scales, pertaining to many biomedical fields. Therefore, understanding cancer is necessarily an interdisciplinary task that requires placing specialised experimental and clinical research into a broader conceptual, theoretical, and methodological framework. Without such a framework, oncology will collect piecemeal results, with scant dialogue between the different scientific communities studying cancer. We argue that one important way forward in service of a more successful dialogue is through greater integration of applied sciences (experimental and clinical) with conceptual and theoretical approaches, informed by philosophical methods. By way of illustration, we explore six central themes: (i) the role of mutations in cancer; (ii) the clonal evolution of cancer cells; (iii) the relationship between cancer and multicellularity; (iv) the tumour microenvironment; (v) the immune system; and (vi) stem cells. In each case, we examine open questions in the scientific literature through a philosophical methodology and show the benefit of such a synergy for the scientific and medical understanding of cancer. 相似文献
97.
Jean-Charles Guimond Mathieu Lévesque Pierre-Luc Michaud Jérémie Berdugo Kenneth Finnson Anie Philip Stéphane Roy 《BMC developmental biology》2010,10(1):15
Background
Axolotls have the unique ability, among vertebrates, to perfectly regenerate complex body parts, such as limbs, after amputation. In addition, axolotls pattern developing and regenerating autopods from the anterior to posterior axis instead of posterior to anterior like all tetrapods studied to date. Sonic hedgehog is important in establishing this anterior-posterior axis of limbs in all tetrapods including axolotls. Interestingly, its expression is conserved (to the posterior side of limb buds and blastemas) in axolotl limbs as in other tetrapods. It has been suggested that BMP-2 may be the secondary mediator of sonic hedgehog, although there is mounting evidence to the contrary in mice. Since BMP-2 expression is on the anterior portion of developing and regenerating limbs prior to digit patterning, opposite to the expression of sonic hedgehog, we examined whether BMP-2 expression was dependent on sonic hedgehog signaling and whether it affects patterning of the autopod during regeneration. 相似文献98.
99.
N Leblanc K David J Grosclaude J M Pradier H Barbier-Brygoo S Labiau C Perrot-Rechenmann 《The Journal of biological chemistry》1999,274(40):28314-28320
Interactions of a collection of monoclonal antibodies (mAbs) to the recombinant Nicotiana tabacum auxin-binding protein 1 (Nt-abp1) were extensively characterized using surface plasmon resonance. Dynamic interaction studies using combinations of Nt-abp1, synthetic peptides corresponding to conserved sequences within auxin-binding proteins, and the mAbs have shown that a number of the mAbs recognized discontinuous epitopes revealing the junction of distinct domains in the folded protein. In particular, the two putative auxin binding domains and the C terminus of the protein were shown to interact with each other in the folded protein. Using the auxin-induced electrical response of tobacco protoplasts as a functional assay, all the mAbs exhibited either auxin antagonist or hormonomimetic properties. These effects, measured for the first time in homologous conditions, confirm that Nt-abp1 is present at the plasma membrane and is involved in the activation of the auxin-dependent electrical response of tobacco protoplasts. Based on our surface plasmon resonance data, we propose that the key event leading to the activation of this auxin electrical response consists of a conformational change in Nt-abp1. 相似文献
100.