全文获取类型
收费全文 | 87篇 |
免费 | 6篇 |
出版年
2021年 | 1篇 |
2019年 | 1篇 |
2017年 | 3篇 |
2016年 | 3篇 |
2015年 | 6篇 |
2014年 | 8篇 |
2013年 | 5篇 |
2012年 | 10篇 |
2011年 | 3篇 |
2010年 | 2篇 |
2009年 | 8篇 |
2008年 | 4篇 |
2007年 | 3篇 |
2006年 | 4篇 |
2005年 | 4篇 |
2004年 | 1篇 |
2003年 | 1篇 |
2002年 | 2篇 |
2001年 | 2篇 |
2000年 | 1篇 |
1999年 | 1篇 |
1998年 | 3篇 |
1997年 | 1篇 |
1996年 | 3篇 |
1995年 | 3篇 |
1993年 | 1篇 |
1992年 | 1篇 |
1988年 | 1篇 |
1982年 | 2篇 |
1981年 | 1篇 |
1979年 | 2篇 |
1977年 | 2篇 |
排序方式: 共有93条查询结果,搜索用时 15 毫秒
1.
Eberhard Fuchs Jan-Christian Wasmuth Gabriele Flügge Gerald Huether Raphael Troost Jürgen Beyer 《Cellular and molecular neurobiology》1996,16(1):21-37
Summary 1. Corticotropin-releasing factor (CRF) is thought to be involved in the regulation of the diurnal activity of the hypothalamus-pituitary-adrenal
(HPA) axis and to act as a neurotransmitter in the brain. To date it is unknown whether the binding sites of the central CRF
system are subject to diurnal variations.
2. We measured the number of CRF binding sites over the course of a complete 24-hr light-dark cycle in the pituitary, amygdala,
bed nucleus of the stria terminalis (BNST), cingulate cortex, visceral cortex, paraventricular nucleus of the hypothalamus,
hippocampus, and locus ceruleus of rats byin vitro receptor autoradiography with iodinated ovine CRF. A 24-hr time course was also established for plasma CRF and corticosterone.
3. The diurnal pattern of plasma CRF does not correlate with the pattern of plasma corticosterone. Within the brain, CRF binding
in the basolateral nucleus of the amygdala showed a U-shaped curve with maximum levels in the morning and a wide hallow between
1500 and 0100. A biphasic profile with a small depression in the afternoon and a more pronounced depression in the second
half of the activity period is characteristic for the other brain areas and the pituitary. The profile for the pituitary correlates
with those for the BNST and the area of the locus ceruleus. Furthermore, the diurnal pattern of CRF binding sites in the BNST
correlates with that of the hippocampus, and the daytime pattern of the visceral cortex is similar to that of both the hippocampus
and the BNST.
4. Since the CRF-binding profiles in the brain and the pituitary clearly differ from the profiles of both plasma CRF and corticosterone,
one may assume that the diurnal pattern of central CRF binding sites is not directly coupled to the activity of the HPA axis. 相似文献
2.
WhileEscherichia coli is common as a commensal organism in the distal ileum and colon, the presence of colonization factors (CF) on pathogenic strains ofE. coli facilitates attachment of the organism to intestinal receptor molecules in a species- and tissue-specific fashion. After the initial adherence, colonization occurs, and the involvement of additional virulence determinants leads to illness. EnterotoxigenicE. coli (ETEC) is the most extensively studied of the five categories ofE. coli that cause diarrheal disease, and has the greatest impact on health worldwide. ETEC can be isolated from domestic animals and humans. The biochemistry, genetics, epidemiology, antigenic characteristics, and cell and receptor binding properties of ETEC have been extensively described. Another major category, enteropathogenicE. coli (EPEC), has virulence mechanisms, primarily effacement and cytoskeletal rearrangement of intestinal brush borders, that are distinct from ETEC. An EPEC CF receptor has been purified and characterized as a sialidated transmembrane glycoprotein complex directly attached to actin, thereby associating CF-binding with host-cell response. Three, additional categories ofE. coli diarrheal disease, their colonization factors and their host cell receptors are discussed. It appears that biofilms exist in the intestine in a manner similar to oral bacterial biofilms, and thatE. coli is part of these biofilms as both commensals and pathogens.Abbreviations CF
colonization factor
- CFA
Colonization Factor Antigen
- CS
coli-surface-associated antigen
- EAggEC
enteroaggregativeE. coli
- ECDD
E. coli diarrheal disease
- EHEC
enterohemorrhagicE. coli
- EIEC
enteroinvasiveE. coli
- EPEC
enteropathogenicE. coli
- ETEC
enterotoxigenicE. coli
- Gal
galactose
- GalNAc
N-acetyl galactosamine
- LT
heat-labile toxin
- NeuAc
N-acetyl neuraminic acid
- PCF
Putative colonization factor
- RBC
red blood cells
- SLT
Shiga-like toxin
- ST
heat-stable toxin 相似文献
3.
DNA sequences were determined for three to five alleles of the bride-of-
sevenless (boss) gene in each of four species of Drosophila. The product of
boss is a transmembrane receptor for a ligand coded by the sevenless gene
that triggers differentiation of the R7 photoreceptor cell in the compound
eye. Population parameters affecting the rate and pattern of molecular
evolution of boss were estimated from the multinomial configurations of
nucleotide polymorphisms of synonymous codons. The time of divergence
between D. melanogaster and D. simulans was estimated as approximately 1
Myr, that between D. teissieri and D. yakuba as approximately 0.75 Myr, and
that between the two pairs of sibling species as approximately 2 Myr. (The
boss genes themselves have estimated divergence times approximately 50%
greater than the species divergence times.) The effective size of the
species was estimated as approximately 5 x 10(6), and the average mutation
rate was estimated as 1-2 x 10(-9)/nucleotide/generation. The ratio of
amino acid polymorphisms within species to fixed differences between
species suggests that approximately 25% of all possible single-step amino
acid replacements in the boss gene product may be selectively neutral or
nearly neutral. The data also imply that random genetic drift has been
responsible for virtually all of the observed differences in the portion of
the boss gene analyzed among the four species.
相似文献
4.
Evolutionary origin of human and primate malarias: evidence from the circumsporozoite protein gene 总被引:8,自引:1,他引:7
We have analyzed the conserved regions of the gene coding for the
circumsporozoite protein (CSP) in 12 species of Plasmodium, the malaria
parasite. The closest evolutionary relative of P. falciparum, the agent of
malignant human malaria, is P. reichenowi, a chimpanzee parasite. This is
consistent with the hypothesis that P. falciparum is an ancient human
parasite, associated with humans since the divergence of the hominids from
their closest hominoid relatives. Three other human Plasmodium species are
each genetically indistinguishable from species parasitic to nonhuman
primates; that is, for the DNA sequences included in our analysis, the
differences between species are not greater than the differences between
strains of the human species. The human P. malariae is indistinguishable
from P. brasilianum, and P. vivax is indistinguishable from P. simium; P.
brasilianum and P. simium are parasitic to New World monkeys. The human P.
vivax-like is indistinguishable from P. simiovale, a parasite of Old World
macaques. We conjecture that P. malariae, P. vivax, and P. vivax-like are
evolutionarily recent human parasites, the first two at least acquired only
within the last several thousand years, and perhaps within the last few
hundred years, after the expansion of human populations in South America
following the European colonizations. We estimate the rate of evolution of
the conserved regions of the CSP gene as 2.46 x 10(-9) per site per year.
The divergence between the P. falciparum and P. reichenowi lineages is
accordingly dated 8.9 Myr ago. The divergence between the three lineages
leading to the human parasites is very ancient, about 100 Myr old between
P. malariae and P. vivax (and P. vivax-like) and about 165 Myr old between
P. falciparum and the other two.
相似文献
5.
Oligomeric forms of the membrane-bound acetylcholine receptor disclosed upon extraction of the M(r) 43,000 nonreceptor peptide 下载免费PDF全文
FJ Barrantes 《The Journal of cell biology》1982,92(1):60-68
Oligomeric forms of the acetylcholine receptor are directly visualized by electron microscopy in receptor-rich membranes from torpedo marmorata. The receptor structures are quantitatively correlated with the molecular species so far identified only after detergent solubilization, and further related to the polypeptide composition of the membranes and changes thereof. The structural identification is made possibly by the increased fragility of the membranes after extraction of nonreceptor peptides and their subsequent disruption upon drying onto hydrophilic carbon supports. Receptor particles in native membranes depleted of nonreceptor peptides appear as single units of 7-8 nm, and double and multiple aggregates thereof. Particle doublets having a main-axis diameter of 19 +/- 3 nm predominate in these membranes. Linear aggregates of particles similar to those observed in rotary replicas of quick-frozen fresh electrolytes (Heuser, J.E. and S. R. Salpeter. 1979, J. Cell Biol. 82: 150-173) are also present in the alkaline-extracted membranes. Chemical modifications of the thiol groups shift the distribution of structural species. Dithiothreitol reduction, which renders almost exclusively the 9S, monomeric receptor form, results in the observation of the 7-8 nm particle in isolated form. The proportion of doublets increases in membranes alkylated with N-ethylmaleimide. Treatment with 5,5’-dithiobis-(nitrobenzoic acid) increases the proportion of higher oligomeric species, and particle aggregates (n=oligo) predominate. The nonreceptor v-peptide (doublet of M(r) 43,000) appears to play a role in the receptor monomer-polymer equilibria. Receptor protein and v-peptide co-aggregate upon reduction and reoxidation of native membranes. In membranes protected ab initio with N- ethylmaleimide, only the receptor appears to self-aggregate. The v-peptide cannot be extracted from these alkylated membranes, though it is easily released from normal, subsequently alkylated or reduced membranes. A stabilization of the dimeric species by the nonreceptor v-peptide is suggested by these experiments. Monospecific antibodies against the v-peptide are used in conjunction with rhodamine- labeled anti-bodies in an indirect immunoflourescence assay to map the vectorial exposure of the v-peptide. When intact membranes, v-peptide depleted and “holey” native membranes (treated with 0.3 percent saponin) are compared, maximal labeling is obtained with the latter type of membranes, suggesting a predominantly cytoplasmic exposure of the antigenic determinants of the v-peptide in the membrane. The influence of the v-peptide in the thiol-dependent interconversions of the receptor protein and the putative topography of the peptide are analyzed in the light of the present results. 相似文献
6.
Gert Rijksen Gerard E. J. Staal Margreet J. M. van der Vlist Frits A. Beemer Jaap Troost Wolf Gutensohn Jan P. R. M. van Laarhoven Chris H. M. M. de Bruyn 《Human genetics》1981,57(1):39-47
Summary A patient with the full clinical expression of the classical Lesch-Nyhan syndrome is presented with a residual hypoxanthine-guanine phosphoribosyl transferase (HGPRT) activity of 5–10% in erythrocyte lysate and about 30% in fibroblast lysate. The activities of other erythrocyte enzymes of purine metabolism were typical for a classical Lesch-Nyhan patient. The effects of allopurinol therapy on the excretion of urinary purine metabolites were studied by a newly developed isotachophoretic technique.The unusually high residual activity of HGPRT in erythrodytes and fibroblasts of the patient enabled the enzymologic characterization of the mutant enzyme: in fibroblasts the affinities for the substrates hypoxanthine and guanine were normal. However, there was an increased apparent K
m for phosphoribosylpyrophosphate (PRPP), a complete absence of product inhibition by IMP and GMP, and a decreased heat stability. Addition of PRPP did not stabilize the mutant enzyme. In addition to the altered properties of the fibroblast enzyme, the K
m of the erythrocyte enzyme for hypoxanthine was also increased.Immunoprecipitation experiments revealed the presence of an approximately normal amount of material cross-reacting with anti-human HGPRT antiserum. However, it appeared that this cross-reacting material had a decreased stability. When intact erythrocytes were incubated with radiolabeled purine bases, no formation of IMP or GMP could be detected, despite the relatively high residual activity of HGPRT in the hemolysate. The results fit the following hypothesis: as a consequence of a structural mutation affecting the PRPP-site of the enzyme and a decreased heat stability, the activity of the mutant enzyme under in vivo conditions is virtually zero.In the erythrocytes of the patient's mother a normal HGPRT-activity was found. However, the activity in her fibroblasts was lower than normal, while a decreased heat stability and an intermediate behavior towards IMP could be shown.Hair root analysis of several members of the patient's family confirmed the heterozygosity of the mother, whereas no other heterozygotes could be detected. The family anamnesis did not show other cases of Lesch-Nyhan syndrome. These findings were taken as evidence that the patient described in this paper might represent a mutation orginating from the gametes in either of the maternal grandparents. 相似文献
7.
Vanessa Gonzalez‐Covarrubias Marian Beekman Hae‐Won Uh Adrie Dane Jorne Troost Iryna Paliukhovich Frans M. van der Kloet Jeanine Houwing‐Duistermaat Rob J. Vreeken Thomas Hankemeier Eline P. Slagboom 《Aging cell》2013,12(3):426-434
Middle‐aged offspring of nonagenarians, as compared to their spouses (controls), show a favorable lipid metabolism marked by larger LDL particle size in men and lower total triglyceride levels in women. To investigate which specific lipids associate with familial longevity, we explore the plasma lipidome by measuring 128 lipid species using liquid chromatography coupled to mass spectrometry in 1526 offspring of nonagenarians (59 years ± 6.6) and 675 (59 years ± 7.4) controls from the Leiden Longevity Study. In men, no significant differences were observed between offspring and controls. In women, however, 19 lipid species associated with familial longevity. Female offspring showed higher levels of ether phosphocholine (PC) and sphingomyelin (SM) species (3.5–8.7%) and lower levels of phosphoethanolamine PE (38:6) and long‐chain triglycerides (TG) (9.4–12.4%). The association with familial longevity of two ether PC and four SM species was independent of total triglyceride levels. In addition, the longevity‐associated lipid profile was characterized by a higher ratio of monounsaturated (MUFA) over polyunsaturated (PUFA) lipid species, suggesting that female offspring have a plasma lipidome less prone to oxidative stress. Ether PC and SM species were identified as novel longevity markers in females, independent of total triglycerides levels. Several longevity‐associated lipids correlated with a lower risk of hypertension and diabetes in the Leiden Longevity Study cohort. This sex‐specific lipid signature marks familial longevity and may suggest a plasma lipidome with a better antioxidant capacity, lower lipid peroxidation and inflammatory precursors, and an efficient beta‐oxidation function. 相似文献
8.
Elhaseen Elamin Ad Masclee Kati Juuti-Uusitalo Sven van IJzendoorn Freddy Troost Harm-Jan Pieters Jan Dekker Daisy Jonkers 《PloS one》2013,8(3)
Background & Aims
Evidence is accumulating that ethanol and its oxidative metabolite, acetaldehyde, can disrupt intestinal epithelial integrity, an important factor contributing to ethanol-induced liver injury. However, ethanol can also be metabolized non-oxidatively generating phosphatidylethanol and fatty acid ethyl esters (FAEEs). This study aims to investigate the effects of FAEEs on barrier function, and to explore the role of oxidative stress as possible mechanism.Methods
Epithelial permeability was assessed by paracellular flux of fluorescein isothiocyanate-conjugated dextran using live cell imaging. Cell integrity was evaluated by lactate dehydrogenase release. Localization and protein levels of ZO-1 and occludin were analyzed by immunofluorescence and cell-based ELISA, respectively. Intracellular oxidative stress and cellular ATP levels were measured by dichlorofluorescein and luciferase driven bioluminescence, respectively.Results
In vitro, ethyl oleate and ethyl palmitate dose dependently increased permeability associated with disruption and decreased ZO-1 and occludin protein levels, respectively, and increased intracellular oxidative stress without compromising cell viability. These effects could partially be attenuated by pretreatment with the antioxidant, resveratrol, pointing to the role of oxidative stress in the FAEEs-induced intestinal barrier dysfunction.Conclusions
These findings show that FAEEs can induce intestinal barrier dysfunction by disrupting the tight junctions, most likely via reactive oxygen species-dependent mechanism. 相似文献9.
10.
Peggy CR Godschalk Mathijs P Bergman Raymond FJ Gorkink Guus Simons Nicole van den Braak Albert J Lastovica Hubert P Endtz Henri A Verbrugh Alex van Belkum 《BMC microbiology》2006,6(1):32-13