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The very low density lipoprotein receptor (VLDL-r) is a cell-surface molecule specialized for the internalization of multiple diverse ligands, including apolipoprotein E (apoE)-containing lipoprotein particles, via clathrin-coated pits. Its structure is similar to the low-density lipoprotein receptor (LDL-r), although the two have substantially different systemic distributions and regulatory pathways. The present work examines the distribution of VLDL-r in the central nervous system (CNS) and in relation to senile plaques in Alzheimer disease (AD). VLDL-r is present on resting and activated microglia, particularly those associated with senile plaques (SPs). VLDL-r immunoreactivity is also found in cortical neurons. Two exons of VLDL-r mRNA are differentially spliced in the mature receptor mRNA. One set of splice forms gives rise to receptors containing (or lacking) an extracellular O-linked glycosylation domain near the transmembrane portion of the molecule. The other set of splice forms appears to be brain-specific, and is responsible for the presence or absence of one of the cysteine-rich repeat regions in the binding region of the molecule. Ratios of the receptor variants generated from these splice forms do not differ substantially across different cortical areas or in AD. We hypothesize that VLDL-r might contribute to metabolism of apoE and apoE/A beta complexes in the brain. Further characterizations of apoE receptors in Alzheimer brain may help lay the groundwork for understanding the role of apoE in the CNS and in the pathophysiology of AD.  相似文献   
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Phage display has been shown to facilitate greatly the selectionof polypeptides with desired properties by establishing a directlink between the polypeptide and the gene that encodes it. However,selection for catalytic activities displayed on phage remainsa challenge, since reaction products diffuse away from the enzymeand make it difficult to recover catalytically active phage–enzymes.We have recently described a selection methodology in whichthe reaction substrate (and eventually the reaction product)is anchored on calmodulin-tagged phage–enzymes by meansof a calmodulin binding peptide. Phage displaying a catalyticactivity are physically isolated by means of affinity reagentsspecific for the product of reaction. In this study, we investigatedthe efficiency of selection for catalysis by phage display,using a ligase (the Escherichia coli biotin ligase BirA) andan endopeptidase (the rat trypsin His57  相似文献   
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Wei Wen  Andrei Lozzi   《Pattern recognition》1992,25(12):1427-1434
A model-based scene analysis for the recognition of imperfect and possibly occluded two-dimensional (2D) industrial parts is described. The means of recognition leads reliably to the correct association of the sides making up the unknown object to those of the model. Both the scene polygon and the model are divided into pairs of complementary subpolygons. This is done by a cutting line drawn parallel and close to a selected side. The subpolygons from the object are compared to all possible subpolygons from the model. Invariant moments are used in the analysis. A matching process using clusters of mutually consistent features is used to hypothesize the identity of the object. Examples are given to illustrate the method.  相似文献   
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Carbon nanotubes (CNTs) thin films deposited by plasma enhanced chemical vapor deposition have been investigated as resistive gas sensors towards NO2 oxidizing gas. Effects of air oxidative treatment dramatically influence the nanotubes’ electrical resistance as determined by volt-amperometric measurements. In particular the electrical measurements show that electrical behavior of the CNT films can be converted from semiconducting to metallic through thermal treatments in oxygen. The electrical response was then measured exposing the films to sub-ppm NO2 concentrations (100 ppb in air) at 165 °C. Upon exposure to NO2, the electrical resistance of CNTs was found to decrease. The obtained results demonstrate that nanotubes could find use as a sensitive chemical gas sensor for (a) the fast response accompanied by a high sensitivity to sub-ppm NO2 exposure, and (b) the precise recover of the base resistance value in absence of NO2 at a fixed operating temperature, likewise indicating that intrinsic properties measured on as prepared nanotubes may be severely changed by extrinsic oxidative treatment effects.  相似文献   
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Interaction between angiotensin II (Ang II) and the fragment peptide 300-320 (fCT300-320) of the rat angiotensin II receptor AT1a was demonstrated by relaxation measurements, NOE effects, chemical shift variations, and CD measurements. The correlation times modulating dipolar interactions for the bound and free forms of Ang II were estimated by the ratio of the nonselective and single-selective longitudinal relaxation rates. The intermolecular NOEs observed in NOESY spectra between HN protons of 9Lys(fCT) and 6His(ang), 10Phe(fCT) and 8Phe(ang), HN proton of 3Tyr(fCT) and Halpha of 4Tyr(ang), 5Phe(fCT)Hdelta and Halpha of 4Tyr(ang) indicated that Ang II aromatic residues are directly involved in the interaction, as also verified by relaxation data. Some fCT300-320 backbone features were inferred by the CSI method and CD experiments revealing that the presence of Ang II enhances the existential probability of helical conformations in the fCT fragment. Restrained molecular dynamics using the simulated annealing protocol was performed with intermolecular NOEs as constraints, imposing an alpha-helix backbone structure to fCT300-320 fragment. In the built model, one strongly preferred interaction was found that allows intermolecular stacking between aromatic rings and forces the peptide to wrap around the 6Leu side chain of the receptor fragment.  相似文献   
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Background: Basal cell carcinoma is one of the most common types of non-melanoma skin cancers, which can be locally destructive despite low-rate metastasis. Surgery is the treatment of choice, but it lacks of efficacy on advanced cases. Hedgehog pathway inhibitors are a class of drugs providing a new therapeutic option for patients affected by advanced disease. Besides systemic therapy, such as vismodegib and sonidegib, also topical inhibitors have been developed. Patidegib is able to decrease tumor burden, reducing the adverse effects induced by systemic targeted therapies. Methods: We performed comprehensive research to summarize the use of patidegib in advanced and recurrent aggressive basal cell carcinomas. Only English language human studies were included in the search. Results: Seven trials reported the application of patidegib. Both topical and systemic patidegib demonstrated safety, tolerability, and efficacy in naïve patients with stage II and III basal cell carcinomas, while stage IV disease and not-naïve patients did not show any benefit. Conclusion: Unlike systemic Hedgehog pathway inhibitors, patidegib 2% gel is not associated with systemic adverse effects and allows a better patient management. Considering the multidisciplinary management of neoplasia, in the era of precision medicine, it is mandatory to confide in pharmacogenomics to obtain personalized combined or sequential therapies.  相似文献   
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High-quality bulk ZnGa2O4 has been synthesized from equimolar mixtures of ZnO and Ga2O3 by the conventional solid-state method. For the first time, the sample has been characterized in detail to confirm the formation of pure single phase of spinel ZnGa2O4. The formation of ZnGa2O4 has been confirmed by sintering the mixtures of ZnO and Ga2O3 at different temperatures, ranging from 900–1200 °C. It is observed that the single phase of ZnGa2O4 has been formed at and above 1000 °C sintering temperature for 24 h. The crystallinity and phase formation of this single phase has been confirmed by X-ray diffraction. X-ray photoelectron spectroscopic studies have been carried out for bulk ZnGa2O4 sintered at 1000 °C for 24 h which showed 14% Zn, 28% Ga and 58% O, indicating stoichiometric ZnGa2O4. A new parameter, the energetic separation between the Zn 2p3/2 and Ga 2p3/2 peaks, has been used as a sensitive tool to distinguish between a complete formation of ZnGa2O4 compound and a mixture of ZnO and Ga2O3 powders. Surface morphology studies by scanning electron microscopy reveal that the formation of ZnGa2O4 takes place in mosaic rod-like structure. The purity of the compound has also been checked by the energy dispersive X-ray method, indicating the absence of foreign ions and the ratio of zinc to gallium has been calculated and found to be 1 : 2, indicating stoichiometric ZnGa2O4.  相似文献   
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