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1.
Blasig IE Winkler L Lassowski B Mueller SL Zuleger N Krause E Krause G Gast K Kolbe M Piontek J 《Cellular and molecular life sciences : CMLS》2006,63(4):505-514
Tight junctions seal intercellular clefts via membrane-related strands, hence, maintaining important organ functions. We investigated
the self-association of strand-forming transmembrane tight junction proteins. The regulatory tight junction protein occludin
was differently tagged and cotransfected in eucaryotic cells. These occludins colocalized within the plasma membrane of the
same cell, coprecipitated and exhibited fluorescence resonance energy transfer. Differently tagged strand-forming claudin-5
also colocalized in the plasma membrane of the same cell and showed fluorescence resonance energy transfer. This demonstrates
self-association in intact cells both of occludin and claudin-5 in one plasma membrane. In search of dimerizing regions of
occludin, dimerization of its cytosolic C-terminal coiledcoil domain was identified. In claudin-5, the second extracellular
loop was detected as a dimer. Since the transmembrane junctional adhesion molecule also is known to dimerize, the assumption
that homodimerization of transmembrane tight junction proteins may serve as a common structural feature in tight junction
assembly is supported.
Received 6 October 2005; received after revision 14 December 2005; accepted 27 December 2005
†These authors contributed equally to this work. 相似文献
2.
3.
Seventeen subadult, hatchery-reared razorback suckers ( Xyrauchen texanus ; (  ̄x = 456 mm total length) were implanted with sonic transmitters and tracked for 23 months in the lower 89.6 km of the San Juan River (San Juan arm of Lake Powell, Utah). Fish were released at 2 sites, and 9 made extensive up- and downstream movements (  ̄x = 47.8 km; contact was lost with 4, and 4 others presumably died or lost their transmitters). The San Juan arm is primarily inundated canyon; however, most fish contacts occurred in shallow coves and shoreline with thick stands of flooded salt cedar in the upper inflow area. Eight fish frequented the Piute Farms river/lake mixing zone, and at least 4 moved upstream into the San Juan River. Seven fish were found in 2 aggregations in spring (3 fish in Neskahi Bay in 1996 and 4 fish just downstream of Piute Farms in 1997), and these may have been associated with spawning activity. Continued presence of razorback suckers in the Piute Farms area and lower San Juan River suggests the San Juan inflow to Lake Powell could be used as an alternate stocking site for reintroduction efforts. 相似文献
4.
5.
Malaria is a mosquito-borne disease that is transmitted by inoculation of the Plasmodium parasite sporozoite stage. Sporozoites invade hepatocytes, transform into liver stages, and subsequent liver-stage development ultimately results in release of pathogenic merozoites. Liver stages of the parasite are a prime target for malaria vaccines because they can be completely eliminated by sterilizing immune responses, thereby preventing malarial infection. Using expression profiling, we previously identified genes that are only expressed in the pre-erythrocytic stages of the parasite. Here, we show by reverse genetics that one identified gene, UIS3 (upregulated in infective sporozoites gene 3), is essential for early liver-stage development. uis3-deficient sporozoites infect hepatocytes but are unable to establish blood-stage infections in vivo, and thus do not lead to disease. Immunization with uis3-deficient sporozoites confers complete protection against infectious sporozoite challenge in a rodent malaria model. This protection is sustained and stage specific. Our findings demonstrate that a safe and effective, genetically attenuated whole-organism malaria vaccine is possible. 相似文献
6.
The sense of taste provides animals with valuable information about the nature and quality of food. Bitter taste detection functions as an important sensory input to warn against the ingestion of toxic and noxious substances. T2Rs are a family of approximately 30 highly divergent G-protein-coupled receptors (GPCRs) that are selectively expressed in the tongue and palate epithelium and are implicated in bitter taste sensing. Here we demonstrate, using a combination of genetic, behavioural and physiological studies, that T2R receptors are necessary and sufficient for the detection and perception of bitter compounds, and show that differences in T2Rs between species (human and mouse) can determine the selectivity of bitter taste responses. In addition, we show that mice engineered to express a bitter taste receptor in 'sweet cells' become strongly attracted to its cognate bitter tastants, whereas expression of the same receptor (or even a novel GPCR) in T2R-expressing cells resulted in mice that are averse to the respective compounds. Together these results illustrate the fundamental principle of bitter taste coding at the periphery: dedicated cells act as broadly tuned bitter sensors that are wired to mediate behavioural aversion. 相似文献
7.
Mutation of a new gene encoding a putative pyrin-like protein causes familial cold autoinflammatory syndrome and Muckle-Wells syndrome. 总被引:17,自引:0,他引:17
Familial cold autoinflammatory syndrome (FCAS, MIM 120100), commonly known as familial cold urticaria (FCU), is an autosomal-dominant systemic inflammatory disease characterized by intermittent episodes of rash, arthralgia, fever and conjunctivitis after generalized exposure to cold. FCAS was previously mapped to a 10-cM region on chromosome 1q44 (refs. 5,6). Muckle-Wells syndrome (MWS; MIM 191900), which also maps to chromosome 1q44, is an autosomal-dominant periodic fever syndrome with a similar phenotype except that symptoms are not precipitated by cold exposure and that sensorineural hearing loss is frequently also present. To identify the genes for FCAS and MWS, we screened exons in the 1q44 region for mutations by direct sequencing of genomic DNA from affected individuals and controls. This resulted in the identification of four distinct mutations in a gene that segregated with the disorder in three families with FCAS and one family with MWS. This gene, called CIAS1, is expressed in peripheral blood leukocytes and encodes a protein with a pyrin domain, a nucleotide-binding site (NBS, NACHT subfamily) domain and a leucine-rich repeat (LRR) motif region, suggesting a role in the regulation of inflammation and apoptosis. 相似文献
8.
H. Mueller 《Cellular and molecular life sciences : CMLS》1998,54(12):1291-1298
The discovery and cloning of the cytokine tumor necrosis factor α (TNF) gave rise to new hopes for a significant victory in the war against cancer. Preclinical in vitro studies in cell cultures
and in vivo studies in animal models demonstrated the antitumor capacities of TNF. Although clinical studies were largely
made possible by the availability of recombinant TNF, phase I and II clinical trials showed very quickly that the systemic
administration of TNF induced severe side effects mainly due to its pleiotropic action on immunocompetent cells. The clinical
manifestations of the side effects were similar to those observed during a severe infection and inflammation. Very recently,
lessons from these clinical studies yielded refined approaches whereby the toxicity of TNF is limited through local administration,
a combination with other therapeutic regimens and targeted gene therapy. These new approaches are slated for larger clinical
trials and in the near future might demonstrate the limited but powerful usefulness of TNF as an antineoplastic agent for
different types of cancer.
Received 7 September 1998; received after revision 15 October 1998; accepted 15 October 1998 相似文献
9.
Mutations in INVS encoding inversin cause nephronophthisis type 2, linking renal cystic disease to the function of primary cilia and left-right axis determination 总被引:20,自引:0,他引:20
Otto EA Schermer B Obara T O'Toole JF Hiller KS Mueller AM Ruf RG Hoefele J Beekmann F Landau D Foreman JW Goodship JA Strachan T Kispert A Wolf MT Gagnadoux MF Nivet H Antignac C Walz G Drummond IA Benzing T Hildebrandt F 《Nature genetics》2003,34(4):413-420
Nephronophthisis (NPHP), an autosomal recessive cystic kidney disease, leads to chronic renal failure in children. The genes mutated in NPHP1 and NPHP4 have been identified, and a gene locus associated with infantile nephronophthisis (NPHP2) was mapped. The kidney phenotype of NPHP2 combines clinical features of NPHP and polycystic kidney disease (PKD). Here, we identify inversin (INVS) as the gene mutated in NPHP2 with and without situs inversus. We show molecular interaction of inversin with nephrocystin, the product of the gene mutated in NPHP1 and interaction of nephrocystin with beta-tubulin, a main component of primary cilia. We show that nephrocystin, inversin and beta-tubulin colocalize to primary cilia of renal tubular cells. Furthermore, we produce a PKD-like renal cystic phenotype and randomization of heart looping by knockdown of invs expression in zebrafish. The interaction and colocalization in cilia of inversin, nephrocystin and beta-tubulin connect pathogenetic aspects of NPHP to PKD, to primary cilia function and to left-right axis determination. 相似文献
10.
陈述了一种新的模糊逻辑控制方法,它可消除滑动控制所固有的抖动问题。方法的推导是将多开关滑动控制问题简化成等效的单开关问题。控制规律显示它是一种模糊滑动控制的一般方法。文献中的其他方法可由此法导出。模糊推理规则由两个输入变量组成。第一个输入变量是系统状态到所预定的状态空间中的超平面之间的方向距离;第二个输入变量的选择可根据应用而定,例如方向距离的导数、控制设计者所感兴趣的特定变量,或者某些状态变量的加权之和。这个新方法易于在高阶系统中实现,并且可以直接而明确地控制系统的动态过程。它消除了滑动控制和经典模糊滑动控制中的抖动问题。此外。新方法比其他类似方法的控制要简单。稳定性和性能分析显示了此法的有效性。此法已用于一带有典型驱动和反馈传感器的工业直流电机的位置控制之中。 相似文献