全文获取类型
收费全文 | 97篇 |
免费 | 14篇 |
出版年
2022年 | 1篇 |
2021年 | 1篇 |
2020年 | 1篇 |
2019年 | 3篇 |
2017年 | 1篇 |
2016年 | 6篇 |
2015年 | 2篇 |
2014年 | 8篇 |
2013年 | 6篇 |
2012年 | 6篇 |
2011年 | 9篇 |
2010年 | 5篇 |
2009年 | 3篇 |
2008年 | 4篇 |
2007年 | 4篇 |
2006年 | 5篇 |
2005年 | 4篇 |
2004年 | 7篇 |
2003年 | 3篇 |
2001年 | 1篇 |
1999年 | 3篇 |
1998年 | 4篇 |
1996年 | 2篇 |
1995年 | 1篇 |
1994年 | 2篇 |
1992年 | 4篇 |
1991年 | 3篇 |
1990年 | 3篇 |
1989年 | 2篇 |
1988年 | 1篇 |
1985年 | 2篇 |
1984年 | 1篇 |
1983年 | 1篇 |
1982年 | 1篇 |
1976年 | 1篇 |
排序方式: 共有111条查询结果,搜索用时 432 毫秒
51.
Functional variant in a bitter-taste receptor (hTAS2R16) influences risk of alcohol dependence
下载免费PDF全文
![点击此处可从《American journal of human genetics》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Hinrichs AL Wang JC Bufe B Kwon JM Budde J Allen R Bertelsen S Evans W Dick D Rice J Foroud T Nurnberger J Tischfield JA Kuperman S Crowe R Hesselbrock V Schuckit M Almasy L Porjesz B Edenberg HJ Begleiter H Meyerhof W Bierut LJ Goate AM 《American journal of human genetics》2006,78(1):103-111
A coding single-nucleotide polymorphism (cSNP), K172N, in hTAS2R16, a gene encoding a taste receptor for bitter beta -glucopyranosides, shows significant association with alcohol dependence (P = .00018). This gene is located on chromosome 7q in a region reported elsewhere to exhibit linkage with alcohol dependence. The SNP is located in the putative ligand-binding domain and is associated with an increased sensitivity to many bitter beta -glucopyranosides in the presence of the N172 allele. Individuals with the ancestral allele K172 are at increased risk of alcohol dependence, regardless of ethnicity. However, this risk allele is uncommon in European Americans (minor-allele frequency [MAF] 0.6%), whereas 45% of African Americans carry the allele (MAF 26%), which makes it a much more significant risk factor in the African American population. 相似文献
52.
Brian Vad Line Aagot Thomsen Kresten Bertelsen Magnus Franzmann Jan Mondrup Pedersen Søren B. Nielsen Thomas Vosegaard Zuzana Valnickova Troels Skrydstrup Jan J. Enghild Reinhard Wimmer Niels Chr. Nielsen Daniel E. Otzen 《Biochimica et Biophysica Acta - Proteins and Proteomics》2010,1804(4):806-820
Many small cationic peptides, which are unstructured in aqueous solution, have antimicrobial properties. These properties are assumed to be linked to their ability to permeabilize bacterial membranes, accompanied by the transition to an α-helical folding state. Here we show that there is no direct link between folding of the antimicrobial peptide Novicidin (Nc) and its membrane permeabilization. N-terminal acylation with C8–C16 alkyl chains and the inclusion of anionic lipids both increase Nc's ability to form α-helical structure in the presence of vesicles. Nevertheless, both acylation and anionic lipids reduce the extent of permeabilization of these vesicles and lead to slower permeabilization kinetics. Furthermore, acylation significantly decreases antimicrobial activity. Although acyl chains of increasing length also increase the tendency of the peptides to aggregate in solution, this cannot rationalize our results since permeabilization and antimicrobial activities are observed well below concentrations where aggregation occurs. This suggests that significant induction of α-helical structure is not a prerequisite for membrane perturbation in this class of antimicrobial peptides. Our data suggests that for Nc, induction of α-helical structure may inhibit rather than facilitate membrane disruption, and that a more peripheral interaction may be the most efficient permeabilization mechanism. Furthermore, acylation leads to a deeper embedding in the membrane, which could lead to an anti-permeabilizing “plugging” effect. 相似文献
53.
Karina Barbara Andersen Mette Tingleff Skaanild Mads Frost Bertelsen Leon Brimer 《European Journal of Wildlife Research》2010,56(6):915-921
Tissues from two juvenile brown bears (Ursus arctos), suspected to have died from yew (Taxus baccata) toxicosis, were chemically examined using thin layer chromatography and high performance liquid chromatography. Extraction
and analysis were conducted on heart and liver tissue samples as well as stomach content from the two bears and also on fresh
material from an authenticated yew tree which was used as a standard for comparison. The taxine complex comprised of taxine
B, 1-deoxytaxine B, isotaxine B, 2-acetyltaxin B, 1-deoxyisotaxine B, 2-acetylisotaxine B, and cinnamates were detected in
all extracted samples. taxine B and its isomer isotaxine B are the main toxic constituents in yew. The heart, the target organ
of taxine B, is arrested when reaching the lethal tissue concentration of taxine complex. In the present cases, the concentration
in the hearts was found to be 37 and 17 μg taxine complex per gram tissue, respectively. As no further absorption into the
heart occurs following cardiac arrest, the concentration determined is the actual lethal tissue concentration. Yew ingestion
was confirmed by microscopic examination of stomach contents of both bears. Histopathological findings of contraction band
necrosis in heart specimens were also consistent with yew intoxication. 相似文献
54.
Østergaard KH Bertelsen MF Brøndum ET Aalkjaer C Hasenkam JM Smerup M Wang T Nyengaard JR Baandrup U 《Journal of comparative physiology. B, Biochemical, systemic, and environmental physiology》2011,181(5):691-698
Giraffes are the tallest animals on earth and the effects of gravity on their cardiovascular system have puzzled physiologists
for centuries. The authors measured arterial and venous pressure in the foreleg of anesthetized giraffes, suspended in upright
standing position, and determined the ratio between tunica media and lumen areas along the length of the femoral/tibial arteries
in the hindleg. Volume fraction of elastin, density of vasa vasorum and innervations was estimated by stereology. Immunohistological
staining with S100 was used to examine the innervation. The pressure increase in the artery and vein along the foreleg was
not significantly different from what was expected on basis of gravity. The area of the arterial lumen in the hindleg decreased
towards the hoof from 11.2 ± 4.2 to 0.6 ± 0.5 mm2 (n = 10, P = 0.001), but most of this narrowing occurred within 2–4 cm immediately below the knee. This abrupt narrowing was associated
with a marked increase in media to lumen area ratio (from 1.2 ± 0.5 to 7.8 ± 2.5; P = 0.001), and a decrease in mean volume fraction of elastin from 38 ± 6% proximal to the narrowing to 5.8 ± 1.1% distally
(P = 0.001). The narrowing had a six-fold higher innervation density than the immediate distal and proximal regions. The sudden
narrowing was also observed in the hind legs of neonates, indicating that it does not develop as an adaptation to the high
transmural pressure in the standing giraffe. More likely it represents a preadaptation to the high pressures experienced by
adult giraffes. 相似文献
55.
Sérgio A Batista Gifone A Rocha Andreia MC Rocha Ivan EB Saraiva Mônica MDA Cabral Rodrigo C Oliveira Dulciene MM Queiroz 《BMC microbiology》2011,11(1):61
Background
Helicobacter pylori infection is one of the most common infections worldwide and is associated with gastric cancer and peptic ulcer. Bacterial virulence factors such as CagA have been shown to increase the risk of both diseases. Studies have suggested a causal role for CagA EPIYA polymorphisms in gastric carcinogenesis, and it has been shown to be geographically diverse. We studied associations between H. pylori CagA EPIYA patterns and gastric cancer and duodenal ulcer, in an ethnically admixed Western population from Brazil. CagA EPIYA was determined by PCR and confirmed by sequencing. A total of 436 patients were included, being 188 with gastric cancer, 112 with duodenal ulcer and 136 with gastritis. 相似文献56.
The ficolins recognize carbohydrates and acetylated compounds on microorganisms and dying host cells and are able to activate the lectin pathway of the complement system. In humans, three ficolin genes have been identified: FCN1, FCN2 and FCN3, which encode ficolin-1, ficolin-2 and ficolin-3, respectively. Rodents have only two ficolins designated ficolin-A and ficolin-B that are closely related to human ficolin-1, while the rodent FCN3 orthologue is a pseudogene. Ficolin-2 and ficolin-3 have so far only been observed in humans. Thus, we performed a systematic investigation of the FCN genes in non-human primates. The exons and intron-exon boundaries of the FCN1-3 genes were sequenced in the following primate species: chimpanzee, gorilla, orangutan, rhesus macaque, cynomolgus macaque, baboon and common marmoset. We found that the exon organisation of the FCN genes was very similar between all the non-human primates and the human FCN genes. Several variations in the FCN genes were found in more than one primate specie suggesting that they were carried from one species to another including humans. The amino acid diversity of the ficolins among human and non-human primate species was estimated by calculating the Shannon entropy revealing that all three proteins are generally highly conserved. Ficolin-1 and ficolin-2 showed the highest diversity, whereas ficolin-3 was more conserved. Ficolin-2 and ficolin-3 were present in non-human primate sera with the same characteristic oligomeric structures as seen in human serum. Taken together all the FCN genes show the same characteristics in lower and higher primates. The existence of trans-species polymorphisms suggests that different FCN allelic lineages may be passed from ancestral to descendant species. 相似文献
57.
58.
59.
Cbl-dependent ubiquitination is required for progression of EGF receptors into clathrin-coated pits
下载免费PDF全文
![点击此处可从《Molecular biology of the cell》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Stang E Blystad FD Kazazic M Bertelsen V Brodahl T Raiborg C Stenmark H Madshus IH 《Molecular biology of the cell》2004,15(8):3591-3604
Ligand binding causes the EGF receptor (EGFR) to become ubiquitinated by Cbl upon association with the adaptor protein Grb2. We have investigated the role of ubiquitin and Grb2 in ligand-induced endocytosis of the EGFR. Incubation of cells with EGF on ice caused translocation of Grb2 and Cbl from the cytosol to the rim of coated pits. Grb2 with point mutations in both SH3 domains inhibited recruitment of the EGFR to clathrin-coated pits, in a Ras-independent manner. On overexpression of the Cbl-binding protein Sprouty, ubiquitination of the EGFR was inhibited, the EGFR was recruited only to the rim of coated pits, and endocytosis of the EGFR was inhibited. Conjugation-defective ubiquitin similarly inhibited recruitment of EGF-EGFR to clathrin-coated pits. Even though this does not prove that cargo must be ubiquitinated, this indicates the importance of interaction of ubiquitinated protein(s) with proteins harboring ubiquitin-interacting domains. We propose that Grb2 mediates transient anchoring of the EGFR to an Eps15-containing molecular complex at the rim of coated pits and that Cbl-induced ubiquitination of the EGFR allows relocation of EGFR from the rim to the center of clathrin-coated pits. 相似文献
60.
Genome‐wide association studies of alcohol dependence,DSM‐IV criterion count and individual criteria
Dongbing Lai Leah Wetherill Sarah Bertelsen Caitlin E. Carey Chella Kamarajan Manav Kapoor Jacquelyn L. Meyers Andrey P. Anokhin David A. Bennett Kathleen K. Bucholz Katharine K. Chang Philip L. De Jager Danielle M. Dick Victor Hesselbrock John Kramer Samuel Kuperman John I. Nurnberger Towfique Raj Marc Schuckit Denise M. Scott Robert E. Taylor Jay Tischfield Ahmad R. Hariri Howard J. Edenberg Arpana Agrawal Ryan Bogdan Bernice Porjesz Alison M. Goate Tatiana Foroud 《Genes, Brain & Behavior》2019,18(6)
Genome‐wide association studies (GWAS) of alcohol dependence (AD) have reliably identified variation within alcohol metabolizing genes (eg, ADH1B) but have inconsistently located other signals, which may be partially attributable to symptom heterogeneity underlying the disorder. We conducted GWAS of DSM‐IV AD (primary analysis), DSM‐IV AD criterion count (secondary analysis), and individual dependence criteria (tertiary analysis) among 7418 (1121 families) European American (EA) individuals from the Collaborative Study on the Genetics of Alcoholism (COGA). Trans‐ancestral meta‐analyses combined these results with data from 3175 (585 families) African‐American (AA) individuals from COGA. In the EA GWAS, three loci were genome‐wide significant: rs1229984 in ADH1B for AD criterion count (P = 4.16E?11) and Desire to cut drinking (P = 1.21E?11); rs188227250 (chromosome 8, Drinking more than intended, P = 6.72E?09); rs1912461 (chromosome 15, Time spent drinking, P = 1.77E?08). In the trans‐ancestral meta‐analysis, rs1229984 was associated with multiple phenotypes and two additional loci were genome‐wide significant: rs61826952 (chromosome 1, DSM‐IV AD, P = 8.42E?11); rs7597960 (chromosome 2, Time spent drinking, P = 1.22E?08). Associations with rs1229984 and rs18822750 were replicated in independent datasets. Polygenic risk scores derived from the EA GWAS of AD predicted AD in two EA datasets (P < .01; 0.61%‐1.82% of variance). Identified novel variants (ie, rs1912461, rs61826952) were associated with differential central evoked theta power (loss ? gain; P = .0037) and reward‐related ventral striatum reactivity (P = .008), respectively. This study suggests that studying individual criteria may unveil new insights into the genetic etiology of AD liability. 相似文献