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41.
Background
Tight junctions are an intercellular adhesion complex of epithelial and endothelial cells, and form a paracellular barrier that restricts the diffusion of solutes on the basis of size and charge. Tight junctions are formed by multiprotein complexes containing cytosolic and transmembrane proteins. How these components work together to form functional tight junctions is still not well understood and will require a complete understanding of the molecular composition of the junction. 相似文献42.
Piotr Religa Monika K. Grudzinska Krzysztof Bojakowski Joanna Soin Jerzy Nozynski Michal Zakliczynski Zbigniew Gaciong Marian Zembala Cecilia S?derberg-Nauclér 《PloS one》2009,4(1)
Transplant arteriosclerosis is characterized by inflammation and intimal thickening caused by accumulation of smooth muscle cells (SMCs) both from donor and recipient. We assessed the relationship between clinical factors and the presence of host-derived SMCs in 124 myocardial biopsies from 26 consecutive patients who received hearts from opposite-sex donors. Clinical and demographic information was obtained from the patients'' medical records. Host-derived SMCs accounted for 3.35±2.3% of cells in arterioles (range, 0.08–12.51%). As shown by linear regression analysis, an increased number of SMCs was associated with rejection grade (mean, 1.41±1.03, p = 0.034) and the number of leukocytes (19.1±12.7 per 20 high-power fields, p = 0.01). The accumulation of host-derived SMCs was associated with an increased number of leukocytes in the allografts. In vitro, monocyte chemoattractant protein 1 (MCP-1) released from leukocytes was crucial for SMC migration. After heart allotransplantion, mice treated with MCP-1-specific antibodies had significantly fewer host-derived SMCs in the grafts than mice treated with isotypic antibody controls. We conclude that the number of host-derived SMCs in human cardiac allografts is associated with the rejection grade and that MCP-1 may play pivotal role in recruiting host-derived SMCs into cardiac allografts. 相似文献
43.
We examined the co-operativity of ultra-fast folding of a protein and whether the Phi-value analysis of its transition state depended on the location of the optical probe. We incorporated in turn a tryptophan residue into each of the three helices of the B domain of Protein A. Each Trp mutant of the three-helix bundle protein was used as a pseudo-wild-type parent for Phi-analysis in which the intrinsic Trp fluorescence probed the formation of each helix during the transition state. Apart from local effects in the immediate vicinity of the probe, the three separate sets of Phi-values were in excellent agreement, demonstrating the overall co-operativity of folding and the robustness of the Phi-analysis. The transition state of folding of Protein A contains the second helix being well formed with many stabilizing tertiary hydrophobic interactions. In contrast, the first and the third helices are more poorly structured in the transition state. The mechanism of folding thus involves the concurrent formation of secondary and tertiary interactions, and is towards the nucleation-condensation extreme in the nucleation-condensation-framework continuum of mechanism, with helix 2 being the nucleus. We provide an error analysis of Phi-values derived purely from the kinetics of two-state chevron plots. 相似文献
44.
Cyclic 3', 5'-AMP relay dictyostelium discoideum. V. Adaptation of the cAMP signaling response during cAMP stimulation 下载免费PDF全文
In dictyostelium discoideum, extracellular cAMP activates adenylate cyclase, which leads to an increase in intracellular cAMP and the rate of cAMP secretion. The signaling response to a constant cAMP stimulus is terminated after several minutes by an adaptation mechanism. The time- course of adaptation stimuli of 10(-6) or 10(-7) M cAMP was assessed. We used a perfusion technique to deliver defined cAMP stimuli to [(3)H]adenosine-labeled amoebae and monitored their secretion of [(3)H]cAMP. Amoebae were pretreated with 10(-6) or 10(-7) M cAMP to periods of 0.33-12 minutes, and then immediately given test stimuli of 10(-8) M to 2.5 x 10(-7) M cAMP. The response to a given test stimulus was progressively attenuated and finally extinguished as the duration of the pretreatment stimulus increased. During concentration of the test stimulus. The responses to test stimuli of 10(-8), 5 x 10(-8), 10(-7), or 2.5 x 10(-7) M cAMP were extinguished after approximately 1, 2.25,2.5, and 10 min, respectively. 1.5 min of stimulation with 10(-7) M cAMP was necessary to extinguish the response of a test stimulus of 10(-8) M cAMP. Our data suggest that adaptation begins within 20 s of stimulation, rises rapidly for approximately 2.5 min, and reaches a plateau after approximately 10 min. The absolute rate of rise was faster during pretreatment with 10(-6) than with 10(-7) M cAMP. These results support a working hypothesis in which the occupancy of surface cAMP receptors leads to changes in two opposing cellular processes, excitation and adaptation, that control the activity of D. discoideum adenylate cyclase. 相似文献
45.
The geographic apportionment of mitochondrial genetic diversity in east African chimpanzees, Pan troglodytes schweinfurthii 总被引:3,自引:1,他引:2
This study is a geographically systematic genetic survey of the easternmost
subspecies of chimpanzee, Pan troglodytes schweinfurthii. DNA was
noninvasively collected in the form of shed hair from chimpanzees of known
origin in Uganda, Rwanda, Tanzania, and Zaire. Two hundred sixty-two DNA
sequences from hypervariable region 1 of which of the mitochondrial control
region were generated. Eastern chimpanzees display levels of mitochondrial
genetic variation which are low and which are similar to levels observed in
humans (Homo sapiens). Also like humans, between 80% and 90% of the genetic
variability within the eastern chimpanzees is apportioned within
populations. Spatial autocorrelation analysis shows that genetic similarity
between eastern chimpanzees decreases clinically with distance, in a
pattern remarkably similar to one seen for humans separated by equivalent
geographic distances. Eastern chimpanzee mismatch distributions (frequency
distributions of pairwise genetic differences between individuals) are
similar in shape to those for humans, implying similar population histories
of recent demographic expansion. The overall pattern of genetic variability
in eastern chimpanzees is consistent with the hypothesis that the subject
has responded demographically to paleoclimatically driven changes in the
distribution of eastern African forests during the recent Pleistocene.
相似文献
46.
The self-incompatibility phenotype in brassica is altered by the transformation of a mutant S locus receptor kinase 总被引:2,自引:0,他引:2 下载免费PDF全文
The self-incompatible (SI) Brassica napus line W1, which carries the 910 S allele, was transformed with an inactive copy of the 910 S locus receptor kinase (SRK) gene. Two transformed lines were analyzed based on their heritable ability to set self-seed. The first line was virtually completely self-compatible (SC), and reciprocal pollinations with the original W1 line demonstrated that only the stigma side of the SI phenotype was altered. An analysis of the expression of endogenous SRK-910 demonstrated that the mechanism of transgene action is via gene suppression. Furthermore, the expression of the S locus glycoprotein gene present in the 910 allele (SLG-910), SLG-A10, which is derived from a nonfunctional S allele, and an S locus-related gene were also suppressed. When the transgene was crossed into another SI line carrying the A14 S allele, it was also capable of suppressing the expression of the endogenous genes and of making this line SC. The second transgenic line studied was only partly SC. In this case as well, only the stigma phenotype was affected, although no gene suppression was detected for endogenous SRK-910 or SLG-910. In this line, the expression of the transgene most likely was causing the change in phenotype, and no effect was observed when this transgene was crossed into the other SI line. Therefore, this work reinforces the hypothesis that the SRK gene is required, but only for the stigma side of the SI phenotype, and that a single transgene can alter the SI phenotype of more than one S allele. 相似文献
47.
48.
Religa TL 《Journal of biomolecular NMR》2008,40(3):189-202
Two methods are currently available to solve high resolution protein structures—X-ray crystallography and nuclear magnetic
resonance (NMR). Both methods usually produce highly similar structures, but small differences between both solutions are
always observed. Here the raw NMR data as well as the solved NMR structure were compared to the multiple crystal structures
solved for the WT 60 residue three helix bundle engrailed homeodomain (EnHD) and single point mutants. There was excellent
agreement between TALOS-predicted and crystal structure-observed dihedral angles and a good agreement for the 3
J(H
N
H
α
) couplings for the multiple crystal structures. Around 1% of NOEs were violated for any crystal structure, but no NOE was
inconsistent with all of the crystal structures. Violations usually occurred for surface residues or for residues for which
multiple discreet conformations were observed between the crystal structures. Comparison of the disorder shown in the multiple
crystal structures shows little correlation with dynamics under native conditions for this protein. 相似文献
49.
Background
Alignment of RNA secondary structures is important in studying functional RNA motifs. In recent years, much progress has been made in RNA motif finding and structure alignment. However, existing tools either require a large number of prealigned structures or suffer from high time complexities. This makes it difficult for the tools to process RNAs whose prealigned structures are unavailable or process very large RNA structure databases. 相似文献50.
APP intracellular domain formation and unaltered signaling in the presence of familial Alzheimer's disease mutations 总被引:6,自引:0,他引:6
Bergman A Religa D Karlström H Laudon H Winblad B Lannfelt L Lundkvist J Näslund J 《Experimental cell research》2003,287(1):1-9
One of the cardinal neuropathological findings in brains from Alzheimer's disease (AD) patients is the occurrence of amyloid beta-peptide (Abeta) deposits. The gamma-secretase-mediated intramembrane proteolysis event generating Abeta also results in the release of the APP intracellular domain (AICD), which may mediate nuclear signaling. It was recently shown that AICD starts at a position distal to the site predicted from gamma-secretase cleavage within the membrane. This novel site, the epsilon site, is located close to the inner leaflet of the membrane bilayer. The relationship between proteolysis at the gamma and epsilon sites has not been fully characterized. Here we studied AICD signaling in intact cells using a chimeric C99 molecule and a luciferase reporter system. We show that the release of AICD from the membrane takes place in a compartment downstream of the endoplasmic reticulum, is dependent on presenilin proteins, and can be inhibited by treatment with established gamma-secretase inhibitors. Moreover, we find that AICD signaling remains unaltered from C99 derivatives containing mutations associated with increased Abeta42 production and familial AD. These findings indicate that there are very similar routes for Abeta and AICD formation but that FAD-linked mutations in APP primarily affect gamma-secretase-mediated Abeta42 formation, and not AICD signaling. 相似文献