全文获取类型
收费全文 | 129篇 |
免费 | 0篇 |
国内免费 | 1篇 |
专业分类
系统科学 | 2篇 |
理论与方法论 | 2篇 |
现状及发展 | 37篇 |
研究方法 | 26篇 |
综合类 | 62篇 |
自然研究 | 1篇 |
出版年
2021年 | 1篇 |
2020年 | 1篇 |
2019年 | 1篇 |
2018年 | 1篇 |
2017年 | 1篇 |
2016年 | 1篇 |
2015年 | 4篇 |
2014年 | 2篇 |
2013年 | 3篇 |
2012年 | 12篇 |
2011年 | 14篇 |
2010年 | 4篇 |
2008年 | 10篇 |
2007年 | 11篇 |
2006年 | 5篇 |
2005年 | 9篇 |
2004年 | 6篇 |
2003年 | 8篇 |
2002年 | 9篇 |
2001年 | 1篇 |
2000年 | 1篇 |
1992年 | 1篇 |
1991年 | 1篇 |
1990年 | 1篇 |
1989年 | 2篇 |
1985年 | 1篇 |
1981年 | 1篇 |
1980年 | 2篇 |
1978年 | 1篇 |
1976年 | 2篇 |
1975年 | 1篇 |
1974年 | 1篇 |
1972年 | 1篇 |
1971年 | 1篇 |
1970年 | 1篇 |
1969年 | 2篇 |
1968年 | 1篇 |
1964年 | 1篇 |
1956年 | 1篇 |
1955年 | 3篇 |
排序方式: 共有130条查询结果,搜索用时 15 毫秒
61.
The Drosophila immune response against Gram-negative bacteria is mediated by a peptidoglycan recognition protein 总被引:22,自引:0,他引:22
Gottar M Gobert V Michel T Belvin M Duyk G Hoffmann JA Ferrandon D Royet J 《Nature》2002,416(6881):640-644
The antimicrobial defence of Drosophila relies largely on the challenge-induced synthesis of an array of potent antimicrobial peptides by the fat body. The defence against Gram-positive bacteria and natural fungal infections is mediated by the Toll signalling pathway, whereas defence against Gram-negative bacteria is dependent on the Immune deficiency (IMD) pathway. Loss-of-function mutations in either pathway reduce the resistance to corresponding infections. The link between microbial infections and activation of these two pathways has remained elusive. The Toll pathway is activated by Gram-positive bacteria through a circulating Peptidoglycan recognition protein (PGRP-SA). PGRPs appear to be highly conserved from insects to mammals, and the Drosophila genome contains 13 members. Here we report a mutation in a gene coding for a putative transmembrane protein, PGRP-LC, which reduces survival to Gram-negative sepsis but has no effect on the response to Gram-positive bacteria or natural fungal infections. By genetic epistasis, we demonstrate that PGRP-LC acts upstream of the imd gene. The data on PGRP-SA with respect to the response to Gram-positive infections, together with the present report, indicate that the PGRP family has a principal role in sensing microbial infections in Drosophila. 相似文献
62.
63.
64.
65.
Marie Novak 《Cellular and molecular life sciences : CMLS》1976,32(12):1529-1530
Summary Gonadectomy of SWR of both sexes significantly reduced the number of cysticerci ofTaenia crassiceps, 60 days post infection. There was a significant decrease in the total number of larvae and the number of nonbudding individuals, corresponding with increased number of budding larvae. This indicates that the asexual multiplication of cysticerci in populations from gonadectomized mice was inhibited. 相似文献
66.
67.
Bidart M Ricard N Levet S Samson M Mallet C David L Subileau M Tillet E Feige JJ Bailly S 《Cellular and molecular life sciences : CMLS》2012,69(2):313-324
Bone Morphogenetic Protein 9 (BMP9) has been recently found to be the physiological ligand for the activin receptor-like kinase
1 (ALK1), and to be a major circulating vascular quiescence factor. Moreover, a soluble chimeric ALK1 protein (ALK1-Fc) has
recently been developed and showed powerful anti-tumor growth and anti-angiogenic effects. However, not much is known concerning
BMP9. This prompted us to investigate the human endogenous sources of this cytokine and to further characterize its circulating
form(s) and its function. Analysis of BMP9 expression reveals that BMP9 is produced by hepatocytes and intrahepatic biliary
epithelial cells. Gel filtration analysis combined with ELISA and biological assays demonstrate that BMP9 circulates in plasma
(1) as an unprocessed inactive form that can be further activated by furin a serine endoprotease, and (2) as a mature and
fully active form (composed of the mature form associated with its prodomain). Analysis of BMP9 circulating levels during
mouse development demonstrates that BMP9 peaks during the first 3 weeks after birth and then decreases to 2 ng/mL in adulthood.
We also show that circulating BMP9 physiologically induces a constitutive Smad1/5/8 phosphorylation in endothelial cells.
Taken together, our results argue for the role of BMP9 as a hepatocyte-derived factor, circulating in inactive (40%) and active
(60%) forms, the latter constantly activating endothelial cells to maintain them in a resting state. 相似文献
68.
Paternoster L Standl M Chen CM Ramasamy A Bønnelykke K Duijts L Ferreira MA Alves AC Thyssen JP Albrecht E Baurecht H Feenstra B Sleiman PM Hysi P Warrington NM Curjuric I Myhre R Curtin JA Groen-Blokhuis MM Kerkhof M Sääf A Franke A Ellinghaus D Fölster-Holst R Dermitzakis E Montgomery SB Prokisch H Heim K Hartikainen AL Pouta A Pekkanen J Blakemore AI Buxton JL Kaakinen M Duffy DL Madden PA Heath AC Montgomery GW Thompson PJ Matheson MC Le Souëf P;Australian Asthma Genetics Consortium 《Nature genetics》2012,44(2):187-192
Atopic dermatitis (AD) is a commonly occurring chronic skin disease with high heritability. Apart from filaggrin (FLG), the genes influencing atopic dermatitis are largely unknown. We conducted a genome-wide association meta-analysis of 5,606 affected individuals and 20,565 controls from 16 population-based cohorts and then examined the ten most strongly associated new susceptibility loci in an additional 5,419 affected individuals and 19,833 controls from 14 studies. Three SNPs reached genome-wide significance in the discovery and replication cohorts combined, including rs479844 upstream of OVOL1 (odds ratio (OR) = 0.88, P = 1.1 × 10(-13)) and rs2164983 near ACTL9 (OR = 1.16, P = 7.1 × 10(-9)), both of which are near genes that have been implicated in epidermal proliferation and differentiation, as well as rs2897442 in KIF3A within the cytokine cluster at 5q31.1 (OR = 1.11, P = 3.8 × 10(-8)). We also replicated association with the FLG locus and with two recently identified association signals at 11q13.5 (rs7927894; P = 0.008) and 20q13.33 (rs6010620; P = 0.002). Our results underline the importance of both epidermal barrier function and immune dysregulation in atopic dermatitis pathogenesis. 相似文献
69.
Marie Bessec 《Journal of forecasting》2013,32(6):500-511
In recent years, factor models have received increasing attention from both econometricians and practitioners in the forecasting of macroeconomic variables. In this context, Bai and Ng (Journal of Econometrics 2008; 146 : 304–317) find an improvement in selecting indicators according to the forecast variable prior to factor estimation (targeted predictors). In particular, they propose using the LARS‐EN algorithm to remove irrelevant predictors. In this paper, we adapt the Bai and Ng procedure to a setup in which data releases are delayed and staggered. In the pre‐selection step, we replace actual data with estimates obtained on the basis of past information, where the structure of the available information replicates the one a forecaster would face in real time. We estimate on the reduced dataset the dynamic factor model of Giannone et al. (Journal of Monetary Economics 2008; 55 : 665–676) and Doz et al. (Journal of Econometrics 2011; 164 : 188–205), which is particularly suitable for the very short‐term forecast of GDP. A pseudo real‐time evaluation on French data shows the potential of our approach. Copyright © 2013 John Wiley & Sons, Ltd. 相似文献
70.
Yamanouchi J Rainbow D Serra P Howlett S Hunter K Garner VE Gonzalez-Munoz A Clark J Veijola R Cubbon R Chen SL Rosa R Cumiskey AM Serreze DV Gregory S Rogers J Lyons PA Healy B Smink LJ Todd JA Peterson LB Wicker LS Santamaria P 《Nature genetics》2007,39(3):329-337
Autoimmune diseases are thought to result from imbalances in normal immune physiology and regulation. Here, we show that autoimmune disease susceptibility and resistance alleles on mouse chromosome 3 (Idd3) correlate with differential expression of the key immunoregulatory cytokine interleukin-2 (IL-2). In order to test directly that an approximately twofold reduction in IL-2 underpins the Idd3-linked destabilization of immune homeostasis, we show that engineered haplodeficiency of Il2 gene expression not only reduces T cell IL-2 production by twofold but also mimics the autoimmune dysregulatory effects of the naturally occurring susceptibility alleles of Il2. Reduced IL-2 production achieved by either genetic mechanism correlates with reduced function of CD4(+) CD25(+) regulatory T cells, which are critical for maintaining immune homeostasis. 相似文献