全文获取类型
收费全文 | 232篇 |
免费 | 49篇 |
出版年
2021年 | 4篇 |
2020年 | 1篇 |
2019年 | 3篇 |
2018年 | 3篇 |
2017年 | 7篇 |
2016年 | 10篇 |
2015年 | 13篇 |
2014年 | 13篇 |
2013年 | 10篇 |
2012年 | 11篇 |
2011年 | 10篇 |
2010年 | 13篇 |
2009年 | 7篇 |
2008年 | 7篇 |
2007年 | 11篇 |
2006年 | 12篇 |
2005年 | 22篇 |
2004年 | 5篇 |
2003年 | 7篇 |
2002年 | 5篇 |
2001年 | 9篇 |
2000年 | 8篇 |
1999年 | 9篇 |
1998年 | 13篇 |
1997年 | 6篇 |
1996年 | 10篇 |
1995年 | 2篇 |
1994年 | 5篇 |
1993年 | 2篇 |
1992年 | 4篇 |
1991年 | 2篇 |
1990年 | 5篇 |
1989年 | 2篇 |
1988年 | 1篇 |
1987年 | 4篇 |
1986年 | 1篇 |
1982年 | 2篇 |
1981年 | 4篇 |
1980年 | 3篇 |
1979年 | 2篇 |
1978年 | 2篇 |
1977年 | 3篇 |
1975年 | 1篇 |
1974年 | 1篇 |
1973年 | 2篇 |
1972年 | 1篇 |
1969年 | 1篇 |
1965年 | 1篇 |
1934年 | 1篇 |
排序方式: 共有281条查询结果,搜索用时 15 毫秒
1.
2.
3.
4.
5.
David Gendron Anne-Marie Lemay Claudine Tremblay Laetitia JA Lai Anick Langlois émilie Bernatchez Nicolas Flamand Marie-Renée Blanchet Anthony S Don Ynuk Bossé élyse Bissonnette David Marsolais 《Respiratory research》2015,16(1)
Background
In vivo phosphorylation of sphingosine analogs with their ensuing binding and activation of their cell-surface sphingosine-1-phosphate receptors is regarded as the main immunomodulatory mechanism of this new class of drugs. Prophylactic treatment with sphingosine analogs interferes with experimental asthma by impeding the migration of dendritic cells to draining lymph nodes. However, whether these drugs can also alleviate allergic airway inflammation after its onset remains to be determined. Herein, we investigated to which extent and by which mechanisms the sphingosine analog AAL-R interferes with key features of asthma in a murine model during ongoing allergic inflammation induced by Dermatophagoides pteronyssinus.Methods
BALB/c mice were exposed to either D. pteronyssinus or saline, intranasally, once-daily for 10 consecutive days. Mice were treated intratracheally with either AAL-R, its pre-phosphorylated form AFD-R, or the vehicle before every allergen challenge over the last four days, i.e. after the onset of allergic airway inflammation. On day 11, airway responsiveness to methacholine was measured; inflammatory cells and cytokines were quantified in the airways; and the numbers and/or viability of T cells, B cells and dendritic cells were assessed in the lungs and draining lymph nodes.Results
AAL-R decreased airway hyperresponsiveness induced by D. pteronyssinus by nearly 70%. This was associated with a strong reduction of IL-5 and IL-13 levels in the airways and with a decreased eosinophilic response. Notably, the lung CD4+ T cells were almost entirely eliminated by AAL-R, which concurred with enhanced apoptosis/necrosis in that cell population. This inhibition occurred in the absence of dendritic cell number modulation in draining lymph nodes. On the other hand, the pre-phosphorylated form AFD-R, which preferentially acts on cell-surface sphingosine-1-phosphate receptors, was relatively impotent at enhancing cell death, which led to a less efficient control of T cell and eosinophil responses in the lungs.Conclusion
Airway delivery of the non-phosphorylated sphingosine analog, but not its pre-phosphorylated counterpart, is highly efficient at controlling the local T cell response after the onset of allergic airway inflammation. The mechanism appears to involve local induction of lymphocyte apoptosis/necrosis, while mildly affecting dendritic cell and T cell accumulation in draining lymph nodes. 相似文献6.
Jilong Li Jie Hou Lin Sun Jordan Maximillian Wilkins Yuan Lu Chad E. Niederhuth Benjamin Ryan Merideth Thomas P. Mawhinney Valeri V. Mossine C. Michael Greenlief John C. Walker William R. Folk Mark Hannink Dennis B. Lubahn James A. Birchler Jianlin Cheng 《PloS one》2015,10(4)
RNA-Seq techniques generate hundreds of millions of short RNA reads using next-generation sequencing (NGS). These RNA reads can be mapped to reference genomes to investigate changes of gene expression but improved procedures for mining large RNA-Seq datasets to extract valuable biological knowledge are needed. RNAMiner—a multi-level bioinformatics protocol and pipeline—has been developed for such datasets. It includes five steps: Mapping RNA-Seq reads to a reference genome, calculating gene expression values, identifying differentially expressed genes, predicting gene functions, and constructing gene regulatory networks. To demonstrate its utility, we applied RNAMiner to datasets generated from Human, Mouse, Arabidopsis thaliana, and Drosophila melanogaster cells, and successfully identified differentially expressed genes, clustered them into cohesive functional groups, and constructed novel gene regulatory networks. The RNAMiner web service is available at http://calla.rnet.missouri.edu/rnaminer/index.html. 相似文献
7.
R Gon?alves LA Szmuchrowski LS Prado BP Couto JCQ Machado VO Damasceno JA Lamounier 《Biology of sport / Institute of Sport》2015,32(3):255-260
The aim of this study was to assess the suitability of body mass index, waist circumference, waist-to-height ratio and aerobic fitness as predictors of cardiovascular risk factor clustering in children. A cross-sectional study was conducted with 290 school boys and girls from 6 to 10 years old, randomly selected. Blood was collected after a 12-hour fasting period. Blood pressure, waist circumference (WC), height and weight were evaluated according to international standards. Aerobic fitness (AF) was assessed by the 20-metre shuttle-run test. Clustering was considered when three of these factors were present: high systolic or diastolic blood pressure, high low-density lipoprotein (LDL) cholesterol, high triglycerides, high plasma glucose, high insulin concentrations and low high-density lipoprotein (HDL) cholesterol. A ROC curve identified the cut-off points of body mass index (BMI), WC, waist-to-height ratio (WHtR) and AF as predictors of risk factor clustering. BMI, WC and WHR resulted in significant areas under the ROC curves, which was not observed for AF. The anthropometric variables were good predictors of cardiovascular risk factor clustering in both sexes, whereas aerobic fitness should not be used to identify cardiovascular risk factor clustering in these children. 相似文献
8.
Dosage compensation refers to the equal expression between the sexes despite the fact that the dosage of the X chromosome
is different in males and females. In Drosophila there is a twofold upregulation of the single male X. In triple X metafemales, there is also dosage compensation, which occurs
by a two-thirds downregulation. There is a concomitant reduction in expression of many autosomal genes in metafemales. The
male specific lethal (MSL) complex is present on the male X chromosome. Evidence is discussed showing that the MSL complex
sequesters a histone acetyltransferase to the X chromosome to mute an otherwise increased expression by diminishing the histone
acetylation on the autosomes. Several lines of evidence indicate that a constraining activity occurs from the MSL complex
to prevent overcompensation on the X that might otherwise occur from the high level of acetylation present. Together, the
evidence suggests that dosage compensation is a modification of a regulatory inverse dosage effect that is a reflection of
intrinsic gene regulatory mechanisms and that the MSL complex has evolved in reaction in order to equalize the expression
on both the X and autosomes of males and females. 相似文献
9.
The structural and functional aspects of two specific centromeres, one drawn from the animal kingdom (Drosophila) and the other from the plant kingdom (maize), are compared. Both cases illustrate an epigenetic component to centromere
specification. The observations of neocentromeres in Drosophila and inactive centromeres in maize constitute one line of evidence for this hypothesis. Another common feature is the divisibility
of centromere function with reduced stability as the size decreases. The systems differ in that Drosophila has no common sequence repeat at all centromeres, whereas maize has a 150-bp unit present in tandem arrays together with
a centromere-specific transposon, centromere retrotransposon maize, present at all primary constrictions. Aspects of centromere
structure known only from one or the other system might be common to both, namely, the presence of centromere RNAs in the
kinetochore as found in maize and the organization of the centromeric histone 3 in tetrameric nucleosomes. 相似文献
10.
Heterosis 总被引:3,自引:0,他引:3
James A. Birchler Hong Yao Sivanandan Chudalayandi Daniel Vaiman Reiner A. Veitia 《The Plant cell》2010,22(7):2105-2112
Heterosis refers to the phenomenon that progeny of diverse varieties of a species or crosses between species exhibit greater biomass, speed of development, and fertility than both parents. Various models have been posited to explain heterosis, including dominance, overdominance, and pseudo-overdominance. In this Perspective, we consider that it might be useful to the field to abandon these terms that by their nature constrain data interpretation and instead attempt a progression to a quantitative genetic framework involving interactions in hierarchical networks. While we do not provide a comprehensive model to explain the phenomenology of heterosis, we provide the details of what needs to be explained and a direction of pursuit that we feel should be fruitful. 相似文献