全文获取类型
收费全文 | 6711篇 |
免费 | 600篇 |
国内免费 | 3篇 |
专业分类
7314篇 |
出版年
2023年 | 37篇 |
2022年 | 74篇 |
2021年 | 159篇 |
2020年 | 72篇 |
2019年 | 123篇 |
2018年 | 139篇 |
2017年 | 113篇 |
2016年 | 197篇 |
2015年 | 341篇 |
2014年 | 437篇 |
2013年 | 534篇 |
2012年 | 578篇 |
2011年 | 572篇 |
2010年 | 365篇 |
2009年 | 341篇 |
2008年 | 444篇 |
2007年 | 428篇 |
2006年 | 416篇 |
2005年 | 386篇 |
2004年 | 341篇 |
2003年 | 317篇 |
2002年 | 305篇 |
2001年 | 44篇 |
2000年 | 50篇 |
1999年 | 71篇 |
1998年 | 63篇 |
1997年 | 42篇 |
1996年 | 34篇 |
1995年 | 36篇 |
1994年 | 30篇 |
1993年 | 28篇 |
1992年 | 21篇 |
1991年 | 14篇 |
1990年 | 14篇 |
1989年 | 17篇 |
1988年 | 9篇 |
1987年 | 18篇 |
1986年 | 16篇 |
1985年 | 9篇 |
1983年 | 12篇 |
1981年 | 3篇 |
1980年 | 13篇 |
1979年 | 7篇 |
1978年 | 8篇 |
1977年 | 9篇 |
1975年 | 5篇 |
1974年 | 4篇 |
1972年 | 2篇 |
1970年 | 2篇 |
1965年 | 2篇 |
排序方式: 共有7314条查询结果,搜索用时 15 毫秒
871.
Olivier Duron Valérie No?l Karen D. McCoy Matteo Bonazzi Karim Sidi-Boumedine Olivier Morel Fabrice Vavre Lionel Zenner Elsa Jourdain Patrick Durand Céline Arnathau Fran?ois Renaud Jean-Fran?ois Trape Abel S. Biguezoton Julie Cremaschi Muriel Dietrich Elsa Léger Ana?s Appelgren Marlène Dupraz Elena Gómez-Díaz Georges Diatta Guiguigbaza-Kossigan Dayo Hassane Adakal Sébastien Zoungrana Laurence Vial Christine Chevillon 《PLoS pathogens》2015,11(5)
Q fever is a highly infectious disease with a worldwide distribution. Its causative agent, the intracellular bacterium Coxiella burnetii, infects a variety of vertebrate species, including humans. Its evolutionary origin remains almost entirely unknown and uncertainty persists regarding the identity and lifestyle of its ancestors. A few tick species were recently found to harbor maternally-inherited Coxiella-like organisms engaged in symbiotic interactions, but their relationships to the Q fever pathogen remain unclear. Here, we extensively sampled ticks, identifying new and atypical Coxiella strains from 40 of 58 examined species, and used this data to infer the evolutionary processes leading to the emergence of C. burnetii. Phylogenetic analyses of multi-locus typing and whole-genome sequencing data revealed that Coxiella-like organisms represent an ancient and monophyletic group allied to ticks. Remarkably, all known C. burnetii strains originate within this group and are the descendants of a Coxiella-like progenitor hosted by ticks. Using both colony-reared and field-collected gravid females, we further establish the presence of highly efficient maternal transmission of these Coxiella-like organisms in four examined tick species, a pattern coherent with an endosymbiotic lifestyle. Our laboratory culture assays also showed that these Coxiella-like organisms were not amenable to culture in the vertebrate cell environment, suggesting different metabolic requirements compared to C. burnetii. Altogether, this corpus of data demonstrates that C. burnetii recently evolved from an inherited symbiont of ticks which succeeded in infecting vertebrate cells, likely by the acquisition of novel virulence factors. 相似文献
872.
The process of clathrin-mediated endocytosis tightly regulates signaling of the superfamily of seven-transmembrane G protein-coupled receptors (GPCRs). A fundamental question in the cell biology of membrane receptor endocytosis is whether activated receptors can initiate the formation of clathrin-coated pits (CPs) or whether they are simply mobilized to pre-existing CPs. Here, using various approaches, including a dynamic assay to monitor the distribution of CPs and GPCR-beta-arrestin complexes in live HeLa cells, we demonstrate for the first time that activated GPCRs do not initiate the de novo formation of CPs but instead are targeted to pre-existing CPs. 相似文献
873.
874.
Emmanuelle Génin Baptiste Coustet Yannick Allanore Ikue Ito Maria Teruel Arnaud Constantin Thierry Schaeverbeke Adeline Ruyssen-Witrand Shigeto Tohma Alain Cantagrel Olivier Vittecoq Thomas Barnetche Xavier Le Lo?t Patrice Fardellone Hiroshi Furukawa Olivier Meyer Benjamin Fernández-Gutiérrez Alejandro Balsa Miguel A. González-Gay Gilles Chiocchia Naoyuki Tsuchiya Javier Martin Philippe Dieudé 《PloS one》2013,8(4)
Background
BANK1 and BLK belong to the pleiotropic autoimmune genes; recently, epistasis between BANK1 and BLK was detected in systemic lupus erythematosus. Although BLK has been reproducibly identified as a risk factor in rheumatoid arthritis (RA), reports are conflicting about the contribution of BANK1 to RA susceptibility. To ascertain the real impact of BANK1 on RA genetic susceptibility, we performed a large meta-analysis including our original data and tested for an epistatic interaction between BANK1 and BLK in RA susceptibility.Patients and Methods
We investigated data for 1,915 RA patients and 1,915 ethnically matched healthy controls genotyped for BANK1 rs10516487 and rs3733197 and BLK rs13277113. The association of each SNP and RA was tested by logistic regression. Multivariate analysis was then used with an interaction term to test for an epistatic interaction between the SNPs in the 2 genes.Results
None of the SNPs tested individually was significantly associated with RA in the genotyped samples. However, we detected an epistatic interaction between BANK1 rs3733197 and BLK rs13277113 (Pinteraction = 0.037). In individuals carrying the BLK rs13277113 GG genotype, presence of the BANK1 rs3733197 G allele increased the risk of RA (odds ratio 1.21 [95% confidence interval 1.04–1.41], P = 0.015. Combining our results with those of all other studies in a large trans-ethnic meta-analysis revealed an association of the BANK1 rs3733197 G allele and RA (1.11 [1.02–1.21], P = 0.012).Conclusion
This study confirms BANK1 as an RA susceptibility gene and for the first time provides evidence for epistasis between BANK1 and BLK in RA. Our results illustrate the concept of pleiotropic epistatic interaction, suggesting that BANK1 and BLK might play a role in RA pathogenesis. 相似文献875.
876.
Lourdais O Hoffman TC Denardo DF 《Journal of comparative physiology. B, Biochemical, systemic, and environmental physiology》2007,177(5):569-577
Parental care provides considerable benefits to offspring and is widespread among animals, yet it is relatively uncommon among
squamate reptiles (e.g., lizards and snakes). However, all pythonine snakes show extended maternal egg brooding with some
species being facultatively endothermic. While facultative endothermy provides thermal benefits, the presence of brooding
in non-endothermic species suggests other potential benefits of brooding. In this study we experimentally tested the functional
significance of maternal brooding relative to water balance in the children’s python, Antaresia childreni, a small species that does not exhibit facultative endothermy. Clutch evaporative water loss (EWL) was positively correlated
with clutch mass and was much lower than expected values based on individual eggs. The conglomerate clutch behaved as a single
unit with a decreasing surface area to volume ratio as clutch size increased. Maternal brooding had a dramatic impact on evaporation
from eggs, reducing and possibly eliminating clutch EWL. In a separate experiment, we found that viability of unattended eggs
is highly affected by humidity level, even in the narrow range from 75 to 100% relative humidity at 30.5°C (20–33 mg m−3 absolute humidity). However, the presence of the brooding female ameliorated this sensitivity, as viability of brooded clutches
at 75% relative humidity was higher than that of non-brooded eggs at either the same absolute humidity or at near-saturated
conditions. Overall, these results demonstrate that brooding behavior strongly promotes egg water balance (and thus egg viability)
in children’s pythons. 相似文献
877.
Moura DS Sultan S Georgin-Lavialle S Barete S Lortholary O Gaillard R Hermine O 《PloS one》2012,7(6):e39468
Mastocytosis is a heterogeneous disease characterized by mast cells accumulation in one or more organs. We have reported that depression is frequent in mastocytosis, but although it was already described, little is known about the prevalence and features of cognitive impairment. Our objective was to describe the prevalence and features of cognitive impairment in a large cohort of patients with this rare disease (n?=?57; mean age?=?45) and to explore the relations between memory impairment and depression. Objective memory impairment was evaluated using the 3(rd) edition of the Clinical Memory scale of Wechsler. Depression symptoms were evaluated using the Hamilton Depression Rating Scale. Age and education levels were controlled for all patients. Patients with mastocytosis presented high levels of cognitive impairment (memory and/or attention) (n?=?22; 38.6%). Cognitive impairment was moderate in 59% of the cases, concerned immediate auditory (41%) and working memory (73%) and was not associated to depression (p≥0.717). In conclusion, immediate auditory memory and attention impairment in mastocytosis are frequent, even in young individuals, and are not consecutive to depression. In mastocytosis, cognitive complaints call for complex neuropsychological assessment. Mild-moderate cognitive impairment and depression constitute two specific but somewhat independent syndromes in mastocytosis. These results suggest differential effects of mast-cell activity in the brain, on systems involved in emotionality and in cognition. 相似文献
878.
CP Gómez M Tiemi Shio P Duplay M Olivier A Descoteaux 《Journal of immunology (Baltimore, Md. : 1950)》2012,189(5):2203-2210
The process of phagocytosis and phagosome maturation involves the recruitment of effector proteins that participate in phagosome formation and in the acidification and/or fusion with various endocytic vesicles. In the current study, we investigated the role of the Src homology region 2 domain-containing phosphatase 1 (SHP-1) in phagolysosome biogenesis. To this end, we used immortalized bone marrow macrophages derived from SHP-1-deficient motheaten mice and their wild-type littermates. We found that SHP-1 is recruited early and remains present on phagosomes for up to 4 h postphagocytosis. Using confocal immunofluorescence microscopy and Western blot analyses on purified phagosome extracts, we observed an impaired recruitment of lysosomal-associated membrane protein 1 in SHP-1-deficient macrophages. Moreover, Western blot analyses revealed that whereas the 51-kDa procathepsin D is recruited to phagosomes, it is not processed into the 46-kDa cathepsin D in the absence of SHP-1, suggesting a defect in acidification. Using the lysosomotropic agent LysoTracker as an indicator of phagosomal pH, we obtained evidence that in the absence of SHP-1, phagosome acidification was impaired. Taken together, these results are consistent with a role for SHP-1 in the regulation of signaling or membrane fusion events involved in phagolysosome biogenesis. 相似文献
879.
Ami Cohen Timothy W. Whitfield Max Kreifeldt Pascale Koebel Brigitte L. Kieffer Candice Contet Olivier George George F. Koob 《PloS one》2014,9(5)
Dynorphins, endogenous opioid peptides that arise from the precursor protein prodynorphin (Pdyn), are hypothesized to be involved in the regulation of mood states and the neuroplasticity associated with addiction. The current study tested the hypothesis that dynorphin in the nucleus accumbens (NAcc) mediates such effects. More specifically, we examined whether knockdown of Pdyn within the NAcc in rats would alter the expression of depressive-like and anxiety-like behavior, as well as cocaine locomotor sensitization. Wistar rats were injected with adeno-associated viral (AAV) vectors encoding either a Pdyn-specific short hairpin RNA (AAV-shPdyn) or a scrambled shRNA (AAV-shScr) as control. Four weeks later, rats were tested for anxiety-like behavior in the elevated plus maze test and depressive-like behavior in the forced swim test (FST). Finally, rats received one daily injection of saline or cocaine (20 mg/kg, i.p.), followed by assessment of locomotion for 4 consecutive days. Following 3 days of abstinence, the rats completed 2 additional daily cocaine/saline locomotor trials. Pdyn knockdown in the NAcc led to a significant reduction in depressive-like behavior in the FST, but had no effect on anxiety-like behavior in the elevated plus maze. Pdyn knockdown did not alter baseline locomotor behavior, the locomotor response to acute cocaine, or the initial sensitization of the locomotor response to cocaine over the first 4 cocaine treatment days. However, following 3 days abstinence the locomotor response to the cocaine challenge returned to their original levels in the AAV-shPdyn rats while remaining heightened in the AAV-shScr rats. These results suggest that dynorphin in a very specific area of the nucleus accumbens contributes to depressive-like states and may be involved in neuroadaptations in the NAcc that contribute to the development of cocaine addiction as a persistent and lasting condition. 相似文献
880.
The Arabidopsis Abscisic Acid Catabolic Gene CYP707A2 Plays a Key Role in Nitrate Control of Seed Dormancy 下载免费PDF全文