全文获取类型
收费全文 | 1052篇 |
免费 | 106篇 |
专业分类
1158篇 |
出版年
2024年 | 1篇 |
2023年 | 12篇 |
2022年 | 20篇 |
2021年 | 42篇 |
2020年 | 33篇 |
2019年 | 31篇 |
2018年 | 38篇 |
2017年 | 41篇 |
2016年 | 45篇 |
2015年 | 86篇 |
2014年 | 84篇 |
2013年 | 111篇 |
2012年 | 114篇 |
2011年 | 98篇 |
2010年 | 55篇 |
2009年 | 48篇 |
2008年 | 58篇 |
2007年 | 45篇 |
2006年 | 38篇 |
2005年 | 35篇 |
2004年 | 33篇 |
2003年 | 19篇 |
2002年 | 14篇 |
2001年 | 7篇 |
2000年 | 4篇 |
1999年 | 9篇 |
1998年 | 4篇 |
1997年 | 3篇 |
1995年 | 1篇 |
1994年 | 2篇 |
1993年 | 1篇 |
1992年 | 2篇 |
1991年 | 5篇 |
1990年 | 2篇 |
1989年 | 4篇 |
1988年 | 1篇 |
1987年 | 2篇 |
1986年 | 3篇 |
1985年 | 2篇 |
1983年 | 1篇 |
1982年 | 1篇 |
1978年 | 1篇 |
1972年 | 1篇 |
1936年 | 1篇 |
排序方式: 共有1158条查询结果,搜索用时 15 毫秒
91.
Background
Seven donkey breeds are recognized by the French studbook. Individuals from the Pyrenean, Provence, Berry Black, Normand, Cotentin and Bourbonnais breeds are characterized by a short coat, while those from the Poitou breed (Baudet du Poitou) are characterized by a long-hair phenotype. We hypothesized that loss-of-function mutations in the FGF5 (fibroblast growth factor 5) gene, which are associated with a long-hair phenotype in several mammalian species, may account for the special coat feature of Poitou donkeys. To the best of our knowledge, mutations in FGF5 have never been described in Equidae.Methods
We sequenced the FGF5 gene from 35 long-haired Poitou donkeys, as well as from a panel of 67 short-haired donkeys from the six other French breeds and 131 short-haired ponies and horses.Results
We identified a recessive c.433_434delAT frameshift deletion in FGF5, present in Poitou and three other donkey breeds and a recessive nonsense c.245G > A substitution, present in Poitou and four other donkey breeds. The frameshift deletion was associated with the long-hair phenotype in Poitou donkeys when present in two copies (n = 31) or combined with the nonsense mutation (n = 4). The frameshift deletion led to a stop codon at position 159 whereas the nonsense mutation led to a stop codon at position 82 in the FGF5 protein. In silico, the two truncated FGF5 proteins were predicted to lack the critical β strands involved in the interaction between FGF5 and its receptor, a mandatory step to inhibit hair growth.Conclusions
Our results highlight the allelic heterogeneity of the long-hair phenotype in donkeys and enlarge the panel of recessive FGF5 loss-of-function alleles described in mammals. Thanks to the DNA test developed in this study, breeders of non-Poitou breeds will have the opportunity to identify long-hair carriers in their breeding stocks.Electronic supplementary material
The online version of this article (doi:10.1186/s12711-014-0065-5) contains supplementary material, which is available to authorized users. 相似文献92.
Evidence of land‐sea transfer of the zoonotic pathogen Campylobacter to a wildlife marine sentinel species 下载免费PDF全文
Johanna L. Baily Guillaume Méric Sion Bayliss Geoffrey Foster Simon E. Moss Eleanor Watson Ben Pascoe Jane Mikhail Romain Pizzi Robert J. Goldstone David G. E. Smith Kim Willoughby Ailsa J. Hall Mark P. Dagleish 《Molecular ecology》2015,24(1):208-221
Environmental pollution often accompanies the expansion and urbanization of human populations where sewage and wastewaters commonly have an impact on the marine environments. Here, we explored the potential for faecal bacterial pathogens, of anthropic origin, to spread to marine wildlife in coastal areas. The common zoonotic bacterium Campylobacter was isolated from grey seals (Halichoerus grypus), an important sentinel species for environmental pollution, and compared to isolates from wild birds, agricultural sources and clinical samples to characterize possible transmission routes. Campylobacter jejuni was present in half of all grey seal pups sampled (24/50 dead and 46/90 live pups) in the breeding colony on the Isle of May (Scotland), where it was frequently associated with histological evidence of disease. Returning yearling animals (19/19) were negative for C. jejuni suggesting clearance of infection while away from the localized colony infection source. The genomes of 90 isolates from seals were sequenced and characterized using a whole‐genome multilocus sequence typing (MLST) approach and compared to 192 published genomes from multiple sources using population genetic approaches and a probabilistic genetic attribution model to infer the source of infection from MLST data. The strong genotype‐host association has enabled the application of source attribution models in epidemiological studies of human campylobacteriosis, and here assignment analyses consistently grouped seal isolates with those from human clinical samples. These findings are consistent with either a common infection source or direct transmission of human campylobacter to grey seals, raising concerns about the spread of human pathogens to wildlife marine sentinel species in coastal areas. 相似文献
93.
Loiseau C Zoorob R Robert A Chastel O Julliard R Sorci G 《Proceedings. Biological sciences / The Royal Society》2011,278(1709):1264-1272
Antagonistic coevolution between hosts and parasites has been proposed as a mechanism maintaining genetic diversity in both host and parasite populations. In particular, the high level of genetic diversity usually observed at the major histocompatibility complex (MHC) is generally thought to be maintained by parasite-driven selection. Among the possible ways through which parasites can maintain MHC diversity, diversifying selection has received relatively less attention. This hypothesis is based on the idea that parasites exert spatially variable selection pressures because of heterogeneity in parasite genetic structure, abundance or virulence. Variable selection pressures should select for different host allelic lineages resulting in population-specific associations between MHC alleles and risk of infection. In this study, we took advantage of a large survey of avian malaria in 13 populations of the house sparrow (Passer domesticus) to test this hypothesis. We found that (i) several MHC alleles were either associated with increased or decreased risk to be infected with Plasmodium relictum, (ii) the effects were population specific, and (iii) some alleles had antagonistic effects across populations. Overall, these results support the hypothesis that diversifying selection in space can maintain MHC variation and suggest a pattern of local adaptation where MHC alleles are selected at the local host population level. 相似文献
94.
95.
Yenny Saraswati Peter Sedman Rebecca Sedman Andika Pandu Wibisono Citrakasih Nente Meuthya Sr Simatupang Ian Singleton Romain Pizzi 《Journal of medical primatology》2019,48(1):65-67
A Delorme's procedure perineal surgical repair was performed in a wild adult male Sumatran orangutan (Pongo abelii) with a chronic persistent rectal prolapse that had been unsuccessfully treated by 6 previous surgeries. The rectal prolapse did not recur, and the orangutan was successfully released to the wild, 6 weeks later. 相似文献
96.
Stéphane Grison Gaëlle Favé Matthieu Maillot Line Manens Olivia Delissen Eric Blanchardon Nathalie Banzet Catherine Defoort Romain Bott Isabelle Dublineau Jocelyne Aigueperse Patrick Gourmelon Jean-Charles Martin Maâmar Souidi 《Metabolomics : Official journal of the Metabolomic Society》2013,9(6):1168-1180
Because uranium is a natural element present in the earth’s crust, the population may be chronically exposed to low doses of it through drinking water. Additionally, the military and civil uses of uranium can also lead to environmental dispersion that can result in high or low doses of acute or chronic exposure. Recent experimental data suggest this might lead to relatively innocuous biological reactions. The aim of this study was to assess the biological changes in rats caused by ingestion of natural uranium in drinking water with a mean daily intake of 2.7 mg/kg for 9 months and to identify potential biomarkers related to such a contamination. Subsequently, we observed no pathology and standard clinical tests were unable to distinguish between treated and untreated animals. Conversely, LC–MS metabolomics identified urine as an appropriate biofluid for discriminating the experimental groups. Of the 1,376 features detected in urine, the most discriminant were metabolites involved in tryptophan, nicotinate, and nicotinamide metabolic pathways. In particular, N-methylnicotinamide, which was found at a level seven times higher in untreated than in contaminated rats, had the greatest discriminating power. These novel results establish a proof of principle for using metabolomics to address chronic low-dose uranium contamination. They open interesting perspectives for understanding the underlying biological mechanisms and designing a diagnostic test of exposure. 相似文献
97.
Romain Duroux Nicolas Renault Joana Esteves Cuelho Laurence Agouridas David Blum Luisa V. Lopes 《Journal of enzyme inhibition and medicinal chemistry》2017,32(1):850-864
The development of adenosine A2A receptor antagonists has received much interest in recent years for the treatment of neurodegenerative diseases. Based on docking studies, a new series of 2-arylbenzoxazoles has been identified as potential A2AR antagonists. Structure-affinity relationship was investigated in position 2, 5 and 6 of the benzoxazole heterocycle leading to compounds with a micromolar affinity towards the A2A receptor. Compound F1, with an affinity of 1?μm, presented good absorption, distribution, metabolism and excretion properties with an excellent aqueous solubility (184?μm) without being cytotoxic at 100?μm. This compound, along with low-molecular weight compound D1 (Ki?=?10?μm), can be easily modulated and thus considered as relevant starting points for further hit-to-lead optimisation. 相似文献
98.
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
99.
Whole-genome comparison of leucine-rich repeat extensins in Arabidopsis and rice. A conserved family of cell wall proteins form a vegetative and a reproductive clade 下载免费PDF全文
Baumberger N Doesseger B Guyot R Diet A Parsons RL Clark MA Simmons MP Bedinger P Goff SA Ringli C Keller B 《Plant physiology》2003,131(3):1313-1326
We have searched the Arabidopsis and rice (Oryza sativa) genomes for homologs of LRX1, an Arabidopsis gene encoding a novel type of cell wall protein containing a leucine-rich repeat (LRR) and an extensin domain. Eleven and eight LRX (LRR/EXTENSIN) genes have been identified in these two plant species, respectively. The LRX gene family encodes proteins characterized by a short N-terminal domain, a domain with 10 LRRs, a cysteine-rich motif, and a variable C-terminal extensin-like domain. Phylogenetic analysis performed on the conserved domains indicates the existence of two major clades of LRX proteins that arose before the eudicot/monocot divergence and then diversified independently in each lineage. In Arabidopsis, gene expression studies by northern hybridization and promoter::uidA fusions showed that the two phylogenetic clades represent a specialization into "reproductive" and "vegetative" LRXs. The four Arabidopsis genes of the "reproductive" clade are specifically expressed in pollen, whereas the seven "vegetative" genes are predominantly expressed in various sporophytic tissues. This separation into two expression classes is also supported by previous studies on maize (Zea mays) and tomato (Lycopersicon esculentum) LRX homologs and by information on available rice ESTs. The strong conservation of the amino acids responsible for the putative recognition specificity of the LRR domain throughout the family suggests that the LRX proteins interact with similar ligands. 相似文献
100.