全文获取类型
收费全文 | 223篇 |
免费 | 35篇 |
专业分类
258篇 |
出版年
2022年 | 1篇 |
2021年 | 4篇 |
2020年 | 2篇 |
2019年 | 3篇 |
2018年 | 3篇 |
2017年 | 2篇 |
2016年 | 4篇 |
2015年 | 4篇 |
2014年 | 10篇 |
2013年 | 7篇 |
2012年 | 14篇 |
2011年 | 18篇 |
2010年 | 23篇 |
2009年 | 13篇 |
2008年 | 9篇 |
2007年 | 12篇 |
2006年 | 12篇 |
2005年 | 10篇 |
2004年 | 12篇 |
2003年 | 10篇 |
2002年 | 8篇 |
2001年 | 4篇 |
2000年 | 9篇 |
1999年 | 6篇 |
1998年 | 5篇 |
1997年 | 3篇 |
1996年 | 3篇 |
1995年 | 1篇 |
1994年 | 3篇 |
1992年 | 3篇 |
1991年 | 2篇 |
1990年 | 3篇 |
1989年 | 1篇 |
1988年 | 5篇 |
1987年 | 2篇 |
1986年 | 4篇 |
1985年 | 4篇 |
1983年 | 1篇 |
1982年 | 2篇 |
1979年 | 4篇 |
1978年 | 2篇 |
1977年 | 4篇 |
1976年 | 1篇 |
1974年 | 1篇 |
1973年 | 1篇 |
1969年 | 1篇 |
1966年 | 1篇 |
1961年 | 1篇 |
排序方式: 共有258条查询结果,搜索用时 0 毫秒
31.
A. Basler 《Human genetics》1978,42(1):26-27
Summary 100 mg INH/kg body weight was administered to male Wistar rats five times, at 24 h intervals, either intraperitoneally or intravenously. In both experimental series the yield of chromosome aberrations in bone marrow cells was not increased as compared to controls. 相似文献
32.
F Zeidán-Chuliá B-HN de Oliveira A B Salmina M F Casanova D P Gelain M Noda A Verkhratsky J CF Moreira 《Cell death & disease》2014,5(5):e1250
Autism and Alzheimer''s disease (AD) are, respectively, neurodevelopmental and degenerative diseases with an increasing epidemiological burden. The AD-associated amyloid-β precursor protein-α has been shown to be elevated in severe autism, leading to the ‘anabolic hypothesis'' of its etiology. Here we performed a focused microarray analysis of genes belonging to NOTCH and WNT signaling cascades, as well as genes related to AD and apoptosis pathways in cerebellar samples from autistic individuals, to provide further evidence for pathological relevance of these cascades for autism. By using the limma package from R and false discovery rate, we demonstrated that 31% (116 out of 374) of the genes belonging to these pathways displayed significant changes in expression (corrected P-values <0.05), with mitochondria-related genes being the most downregulated. We also found upregulation of GRIN1, the channel-forming subunit of NMDA glutamate receptors, and MAP3K1, known activator of the JNK and ERK pathways with anti-apoptotic effect. Expression of PSEN2 (presinilin 2) and APBB1 (or F65) were significantly lower when compared with control samples. Based on these results, we propose a model of NMDA glutamate receptor-mediated ERK activation of α-secretase activity and mitochondrial adaptation to apoptosis that may explain the early brain overgrowth and disruption of synaptic plasticity and connectome in autism. Finally, systems pharmacology analyses of the model that integrates all these genes together (NOWADA) highlighted magnesium (Mg2+) and rapamycin as most efficient drugs to target this network model in silico. Their potential therapeutic application, in the context of autism, is therefore discussed. 相似文献
33.
Hall GL Logie KM Parsons F Schulzke SM Nolan G Murray C Ranganathan S Robinson P Sly PD Stick SM;AREST CF Berry L Garratt L Massie J Mott L Poreddy S Simpson S 《PloS one》2011,6(8):e23932
Background
In school-aged children with cystic fibrosis (CF) structural lung damage assessed using chest CT is associated with abnormal ventilation distribution. The primary objective of this analysis was to determine the relationships between ventilation distribution outcomes and the presence and extent of structural damage as assessed by chest CT in infants and young children with CF.Methods
Data of infants and young children with CF diagnosed following newborn screening consecutively reviewed between August 2005 and December 2009 were analysed. Ventilation distribution (lung clearance index and the first and second moment ratios [LCI, M1/M0 and M2/M0, respectively]), chest CT and airway pathology from bronchoalveolar lavage were determined at diagnosis and then annually. The chest CT scans were evaluated for the presence or absence of bronchiectasis and air trapping.Results
Matched lung function, chest CT and pathology outcomes were available in 49 infants (31 male) with bronchiectasis and air trapping present in 13 (27%) and 24 (49%) infants, respectively. The presence of bronchiectasis or air trapping was associated with increased M2/M0 but not LCI or M1/M0. There was a weak, but statistically significant association between the extent of air trapping and all ventilation distribution outcomes.Conclusion
These findings suggest that in early CF lung disease there are weak associations between ventilation distribution and lung damage from chest CT. These finding are in contrast to those reported in older children. These findings suggest that assessments of LCI could not be used to replace a chest CT scan for the assessment of structural lung disease in the first two years of life. Further research in which both MBW and chest CT outcomes are obtained is required to assess the role of ventilation distribution in tracking the progression of lung damage in infants with CF. 相似文献34.
Background
If biology is modular then clusters, or communities, of proteins derived using only protein interaction network structure should define protein modules with similar biological roles. We investigate the link between biological modules and network communities in yeast and its relationship to the scale at which we probe the network. 相似文献35.
Hardies SC; Martin SL; Voliva CF; Hutchison CA d; Edgell MH 《Molecular biology and evolution》1986,3(2):109-125
36.
8 antioxidants were tested in the SOS chromotest for induction of SOS function and for modulation of benzo[a]pyrene-induced SOS function. None of the antioxidants leads to increased beta-galactosidase activity by itself. Butylated hydroxytoluene at concentrations between 10(-5) M and 3 X 10(-4) M enhances benzo[a]pyrene-induced SOS function at benzo[a]pyrene concentrations between 10(-6) M and 3 X 10(-5) M. Butylated hydroxyanisole, ethoxyquin, propyl gallate and octyl gallate also slightly enhance benzo[a]pyrene-induced SOS function at concentrations up to 3 X 10(-4) M though to a lesser degree than butylated hydroxytoluene. Dodecyl gallate, vitamin C and alpha-tocopherol do not increase benzo[a]pyrene action. In concentrations exceeding 3 X 10(-4) M all synthetic antioxidants tested but not vitamin C and alpha-tocopherol decrease beta-galactosidase activity both in the absence and, more extensively, in the presence of benzo[a]pyrene. Preliminary data suggest that the apparent suppression of benzo[a]pyrene-induced SOS function is not due to an effect on the formation of benzo[a]pyrene metabolites by the metabolizing system used. 相似文献
37.
Cellular splicing factor RAF-2p48/NPI-5/BAT1/UAP56 interacts with the influenza virus nucleoprotein and enhances viral RNA synthesis 总被引:7,自引:0,他引:7 下载免费PDF全文
Momose F Basler CF O'Neill RE Iwamatsu A Palese P Nagata K 《Journal of virology》2001,75(4):1899-1908
Previous biochemical data identified a host cell fraction, designated RAF-2, which stimulated influenza virus RNA synthesis. A 48-kDa polypeptide (RAF-2p48), a cellular splicing factor belonging to the DEAD-box family of RNA-dependent ATPases previously designated BAT1 (also UAP56), has now been identified as essential for RAF-2 stimulatory activity. Additionally, RAF-2p48 was independently identified as an influenza virus nucleoprotein (NP)-interacting protein, NPI-5, in a yeast two-hybrid screen of a mammalian cDNA library. In vitro, RAF-2p48 interacted with free NP but not with NP bound to RNA, and the RAF-2p48-NP complex was dissociated following addition of free RNA. Furthermore, RAF-2p48 facilitated formation of the NP-RNA complexes that likely serve as templates for the viral RNA polymerase. RAF-2p48 was shown, in both in vitro binding assays and the yeast two-hybrid system, to bind to the amino-terminal region of NP, a domain essential for RNA binding. Together, these observations suggest that RAF-2p48 facilitates NP-RNA interaction, thus leading to enhanced influenza virus RNA synthesis. 相似文献
38.
A. J. Driesel K. Römer F. Schunter M. D. Laryea E. M. Schneider P. Wernet J. Henke M. Basler J. Kömpf 《Immunogenetics》1985,21(6):529-538
DNA of unrelated persons as well as members of families that were totally or partially homozygous or completely heterozygous on the loci of the major histocompatibility class I genes has been isolated from peripheral blood lymphocytes and blot hybridized with the class I pseudogene pHLA 12.4 probe. The autoradiographic DNA patterns were discussed and compared with well-defined serological features. Positive associations with serologically typed alleles had been demonstrated for HLA-A1,11 ; -A2; -A3; -B7; -B14; -B35;-Bw41; and -Cw5. 相似文献
39.
40.
Johanna Pott Tina Basler Claudia U. Duerr Manfred Rohde Ralph Goethe Mathias W. Hornef 《Cellular microbiology》2009,11(12):1802-1815
Mycobacterium avium ssp. paratuberculosis (MAP) is the causative agent of Johne's disease, a highly prevalent chronic intestinal infection in domestic and wildlife ruminants. The microbial pathogenesis of MAP infection has attracted additional attention due to an association with the human enteric inflammatory Crohn's disease. MAP is acquired by the faecal–oral route prompting us to study the interaction with differentiated intestinal epithelial cells. MAP was rapidly internalized and accumulated in a late endosomal compartment. In contrast to other opportunistic mycobacteria or M. bovis, MAP induced significant epithelial activation as indicated by a NF-κB-independent but Erk-dependent chemokine secretion. Surprisingly, MAP-induced chemokine production was completely internalization-dependent as inhibition of Rac-dependent bacterial uptake abolished epithelial activation. In accordance, innate immune recognition of MAP by differentiated intestinal epithelial cells occurred through the intracellularly localized pattern recognition receptors toll-like receptor 9 and NOD1 with signal transduction via the adaptor molecules MyD88 and RIP2. The internalization-dependent innate immune activation of intestinal epithelial cells is in contrast to the stimulation of professional phagocytes by extracellular bacterial constituents and might significantly contribute to the histopathological changes observed during enteric MAP infection. 相似文献