全文获取类型
收费全文 | 239篇 |
免费 | 26篇 |
出版年
2023年 | 2篇 |
2021年 | 4篇 |
2020年 | 4篇 |
2019年 | 4篇 |
2018年 | 10篇 |
2017年 | 5篇 |
2016年 | 6篇 |
2015年 | 12篇 |
2014年 | 14篇 |
2013年 | 7篇 |
2012年 | 11篇 |
2011年 | 13篇 |
2010年 | 6篇 |
2009年 | 8篇 |
2008年 | 8篇 |
2007年 | 9篇 |
2006年 | 13篇 |
2005年 | 8篇 |
2004年 | 5篇 |
2003年 | 3篇 |
2002年 | 2篇 |
2001年 | 4篇 |
2000年 | 3篇 |
1999年 | 8篇 |
1998年 | 12篇 |
1997年 | 4篇 |
1996年 | 6篇 |
1995年 | 6篇 |
1994年 | 3篇 |
1993年 | 3篇 |
1992年 | 7篇 |
1991年 | 3篇 |
1990年 | 4篇 |
1989年 | 3篇 |
1988年 | 2篇 |
1985年 | 2篇 |
1983年 | 3篇 |
1982年 | 5篇 |
1981年 | 3篇 |
1979年 | 2篇 |
1978年 | 2篇 |
1977年 | 2篇 |
1976年 | 2篇 |
1975年 | 5篇 |
1974年 | 2篇 |
1973年 | 3篇 |
1970年 | 3篇 |
1959年 | 1篇 |
1954年 | 1篇 |
1934年 | 1篇 |
排序方式: 共有265条查询结果,搜索用时 35 毫秒
1.
Jeff A Johnson Heather RL Lerner Pamela C Rasmussen David P Mindell 《BMC evolutionary biology》2006,6(1):65-12
Background
Populations of the Oriental White-backed Vulture (Gyps bengalensis) have declined by over 95% within the past decade. This decline is largely due to incidental consumption of the non-steroidal anti-inflammatory veterinary pharmaceutical diclofenac, commonly used to treat domestic livestock. The conservation status of other Gyps vultures in southern Asia is also of immediate concern, given the lack of knowledge regarding status of their populations and the continuing existence of taxonomic uncertainties. In this study, we assess phylogenetic relationships for all recognized species and the majority of subspecies within the genus Gyps. The continuing veterinary use of diclofenac is an unknown but potential risk to related species with similar feeding habits to Gyps bengalensis. Therefore, an accurate assessment of the phylogenetic relationships among Gyps vultures should aid in their conservation by clarifying taxonomic uncertainties, and enabling inference of their respective relatedness to susceptible G. bengalensis. 相似文献2.
3.
4.
5.
alpha 1-Proteinase inhibitor (alpha 1-PI), a member of the serine
proteinase inhibitor superfamily, has a primary role in controlling
neutrophil elastase activity within the mammalian circulation. Several
studies have indicated that the reactive center region of alpha 1-PI, the
amino acid sequence of which is critical to recognition of and binding to
target proteinases, is highly divergent within and among species. This
appears to be a consequence of accelerated rates of evolution that may have
been driven by positive Darwinian selection. In order to examine this and
other features of alpha 1-PI evolution in more detail, we have isolated and
sequenced cDNAs representing alpha 1- PI mRNAs of the mouse species Mus
saxicola and Mus minutoides and have compared these with a number of other
mammalian alpha 1-PI mRNAs. Relative to other mammalian mRNAs, the extent
of nonsynonymous substitution is generally high throughout the alpha 1-PI
mRNA molecule, indicating greater overall rates of amino acid substitution.
Within and among mouse species, the 5'-half of the mRNA, but not the
3'-half, has been homogenized by concerted evolution. Finally, the reactive
center is under diversifying or positive Darwinian selection in murid
rodents (rats, mice) and guinea pigs yet is under purifying selection in
primates and artiodactyls. The significance of these findings to alpha 1-PI
function and the possible selective forces driving evolution of serpins in
general are discussed.
相似文献
6.
J. Benitez E. Fernandez P. Garcia Ruiz M. Robledo C. Ramos J. Yebenes 《Human genetics》1994,94(5):563-564
Huntington's disease (HD) is a neurodegenerative and hereditary disease characterized by progressive movement disorders and mental and behavioral abnormalities. The HD gene is an expanding and unstable trinucleotide repeat (CAG repeat sequences). We studied 77 individuals from 38 families with HD in an attempt to obtain information for genetic counselling and differential diagnosis. Our results indicate that individuals with more than 40 repeats will be affected by the disease, whereas those with fewer than 30 will be healthy. There can be some overlap between 30 and 40 repeats, and one should be careful when interpreting these results. 相似文献
7.
Mitochondrial DNA polymorphisms in subterranean mole-rats of the Spalax ehrenbergi superspecies in Israel, and its peripheral isolates 总被引:1,自引:0,他引:1
Nevo E; Honeycutt RL; Yonekawa H; Nelson K; Hanzawa N 《Molecular biology and evolution》1993,10(3):590-604
Patterns of mitochondrial DNA (mtDNA) variation were examined in 133
mole-rats constituting all four chromosomal species (2n = 52, 2n = 54, 2n =
58, and 2n = 60) of the Spalax ehrenbergi superspecies in Israel, as well
as the peripheral isolates of 2n = 60. In the main range of the complex, a
total of 28 mtDNA haplotypes were found in 64 mole-rats, with most
haplotypes being unique to either a single chromosomal species or
population. mtDNA divergence increased from low to high diploid number in a
north-to-south direction in Israel. Overall levels of mtDNA diversity were
unexpectedly the highest in the 2n = 60, the youngest species of the
complex. The mtDNA haplotypes can be separated into two major groups, 2n =
52-54 and 2n = 58-60, and a phylogenetic analysis for each group revealed
evidence of a few haplotypes not sorted by diploid number. The overall
patterns of mtDNA divergence seen within and among the four chromosomal
species are consistent with the parapatric mode of speciation as suggested
from previous studies of allozyme and DNA hybridization. In a separate data
set the patterns of mtDNA variation were examined across the main
geographic range and across peripheral semi-isolates and isolates of the 2n
= 60 chromosomal species. Fifteen haplotypes were found in 69 mole-rats.
High levels of mtDNA diversity characterized the main range, semi-isolated,
and even some desert isolated populations. The peripheral isolates contain
much mtDNA diversity, including novel haplotypes.
相似文献
8.
F. J. Lopez Aparicio F. Zorrilla Benitez F. Santoyo Gonzalez 《Carbohydrate research》1981,90(2):315-318
The homogeneous, neutral polysaccharide isolated from the crude polysaccharide of the fruit pulp from bael (Aegle marmelos) contains arabinose, galactose, and glucose in the molar ratios of 2:3:14. The linkages among the different monosaccharide residues were established through methylation analysis and Smith-degradation studies of the polysaccharide. The anomeric configurations of the different glycosyl groups were determined by study of the chromium trioxide oxidation of the acetylated polysaccharide. Results of these experiments have been discussed in order to assess the structure of the neutral polysaccharide. 相似文献
9.
Maricarmen Hernández‐Rodríguez José Correa‐Basurto Claudia G. Benitez‐Cardoza Aldo Arturo Resendiz‐Albor Martha C. Rosales‐Hernández 《Protein science : a publication of the Protein Society》2013,22(10):1320-1335
The formation of fibrils and oligomers of amyloid beta (Aβ) with 42 amino acid residues (Aβ1–42) is the most important pathophysiological event associated with Alzheimer''s disease (AD). The formation of Aβ fibrils and oligomers requires a conformational change from an α-helix to a β-sheet conformation, which is encouraged by the formation of a salt bridge between Asp 23 or Glu 22 and Lys 28. Recently, Cu2+ and various drugs used for AD treatment, such as galanthamine (Reminyl®), have been reported to inhibit the formation of Aβ fibrils. However, the mechanism of this inhibition remains unclear. Therefore, the aim of this work was to explore how Cu2+ and galanthamine prevent the formation of Aβ1–42 fibrils using molecular dynamics (MD) simulations (20 ns) and in vitro studies using fluorescence and circular dichroism (CD) spectroscopies. The MD simulations revealed that Aβ1–42 acquires a characteristic U-shape before the α-helix to β-sheet conformational change. The formation of a salt bridge between Asp 23 and Lys 28 was also observed beginning at 5 ns. However, the MD simulations of Aβ1−42 in the presence of Cu2+ or galanthamine demonstrated that both ligands prevent the formation of the salt bridge by either binding to Glu 22 and Asp 23 (Cu2+) or to Lys 28 (galanthamine), which prevents Aβ1−42 from adopting the U-characteristic conformation that allows the amino acids to transition to a β-sheet conformation. The docking results revealed that the conformation obtained by the MD simulation of a monomer from the 1Z0Q structure can form similar interactions to those obtained from the 2BGE structure in the oligomers. The in vitro studies demonstrated that Aβ remains in an unfolded conformation when Cu2+ and galanthamine are used. Then, ligands that bind Asp 23 or Glu 22 and Lys 28 could therefore be used to prevent β turn formation and, consequently, the formation of Aβ fibrils. 相似文献
10.
Prasanna M. Chandramouleeswaran Dawen Shen Anna J. Lee Alain Benitez Kara Dods Fiona Gambanga Benjamin J. Wilkins Jamie Merves Yuliana Noah Sarit Toltzis Jennifer H. Yearley Jonathan M. Spergel Hiroshi Nakagawa Rene deWaal Malefyt Amanda B. Muir Mei-Lun Wang 《PloS one》2016,11(3)
Eosinophilic esophagitis (EoE) is a chronic Th2 and food antigen-mediated disease characterized by esophageal eosinophilic infiltration. Thymic stromal lymphopoetin (TSLP), an epithelial derived cytokine which bridges innate and Th2-type adaptive immune responses in other allergic conditions, is overexpressed in esophageal biopsies of EoE subjects. However, the triggers of TSLP expression in the esophageal epithelium are unknown. The objective of the current study was to characterize TSLP expression in human esophageal epithelium in EoE in vivo and to determine the role of food antigens upon epithelial TSLP expression in vitro. Using immunohistochemistry (IHC), we localized TSLP in esophageal biopsies of active EoE (≥15 eos/hpf), inactive EoE (<15 eos/hpf) and non-EoE control subjects, and found that TSLP expression was restricted to the differentiated suprabasal layer of the epithelium in actively inflamed EoE biopsies. Consistent with these results in vivo, inducible TSLP protein secretion was higher in CaCl2 differentiated telomerase-immortalized esophageal epithelial cells (EPC2-hTERT) compared to undifferentiated cells of the basal phenotype, following stimulation with the TLR3 ligand poly(I:C). To determine whether food antigens could directly induce epithelial TSLP secretion, differentiated and undifferentiated primary esophageal epithelial cells from EoE and non-EoE subjects were challenged with food antigens clinically relevant to EoE: Chicken egg ovalbumin (OVA), wheat, and milk proteins beta-lactoglobulin (blg) and beta-casein. Food antigens failed to induce TSLP secretion by undifferentiated cells; in contrast, only OVA induced TSLP secretion in differentiated epithelial cells from both EoE and control cell lines, an effect abolished by budesonide and NF-κb inhibition. Together, our study shows that specific food antigens can trigger innate immune mediated esophageal TSLP secretion, suggesting that esophageal epithelial cells at the barrier surface may play a significant role in the pathogenesis of EoE by regulating TSLP expression. 相似文献