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81.
Here, we identified the mechanisms of action of antidiabetic activity of novel compounds isolated from Cassia fistula stem bark in STZ-diabetic animals. Novel triterpenoid compounds (C1, C2 and C3) were treated to STZ-administered diabetic animals at a concentration of 20mg/kg body weight orally for 60 days to assess their effects on plasma glucose, plasma insulin/C-peptide, serum lipid markers and the enzymes of carbohydrate metabolism, glucose oxidation and insulin signaling molecules. Oral administration of novel triterpenoid compounds to STZ-diabetic animals significantly decreased (p < 0.05) the plasma glucose concentration on the 7th, 15th, 30th, 45th and 60th daysin a duration-dependent manner (p < 0.05). Plasma insulin (p < 0.0001)/C-peptide (p < 0.0006), tissue glycogen (p < 0.0034), glycogen phosphorylase (p < 0.005), glucose 6-phosphatase (p < 0.0001) and lipid markers were significantly increased (p < 0.0001) in diabetic rats, whereas glucokinase (p < 0.0047), glycogen synthase (p < 0.003), glucose oxidation (p < 0.001), GLUT4 mRNA (p < 0.0463), GLUT4 protein (p < 0.0475) and the insulin-signaling molecules IR mRNA (p < 0.0195), IR protein (p < 0.0001), IRS-1 mRNA (p < 0.0478), p-IRS-1Tyr612 (p < 0.0185), Akt mRNA (p < 0.0394), p–AktSer473 (p < 0.0162), GLUT4 mRNA (p < 0.0463) and GLUT4 (p < 0.0475) were decreased in the gastrocnemius muscle. In silico analysis of C1–C3 with IRK and PPAR-γ protein coincided with in vivo findings. C1–C3 possessed promising antidiabetic activity by regulating insulin signaling mechanisms and carbohydrate metabolic enzymes.  相似文献   
82.
Type-2 diabetes mellitus (T2DM), the leading global health burden of this century majorly develops due to obesity and hyperglycemia-induced oxidative stress in skeletal muscles. Hence, developing novel drugs that ameliorate these pathological events is an immediate priority. The study was designed to analyze the possible role of Stevioside, a characteristic sugar from leaves of Stevia rebaudiana (Bertoni) on insulin signaling molecules in gastrocnemius muscle of obesity and hyperglycemia-induced T2DM rats. Adult male Wistar rats rendered diabetic by administration of high fat diet (HFD) and sucrose for 60 days were orally administered with SIT (20 mg/kg/day) for 45 days. Various parameters were estimated including fasting blood glucose (FBG), serum lipid profile, oxidative stress markers, antioxidant enzymes and expression of insulin signaling molecules in diabetic gastrocnemius muscle. Stevioside treatment improved glucose and insulin tolerances in diabetic rats and restored their elevated levels of FBG, serum insulin and lipid profile to normalcy. In diabetic gastrocnemius muscles, Setvioside normalized the altered levels of lipid peroxidase (LPO), hydrogen peroxide (H2O2) and hydroxyl radical (OH*), antioxidant enzymes (CAT, SOD, GPx and GSH) and molecules of insulin signaling including insulin receptor (IR), insulin receptor substrate-1 (IRS-1) and Akt mRNA levels. Furthermore, Stevioside enhanced glucose uptake (GU) and oxidation in diabetic muscles by augmenting glucose transporter 4 (GLUT 4) synthesis very effectively in a similar way to metformin. Results of molecular docking analysis evidenced the higher binding affinity with IRS-1 and GLUT 4. Stevioside effectively inhibits oxidative stress and promotes glucose uptake in diabetic gastrocnemius muscles by activating IR/IRS-1/Akt/GLUT 4 pathway. The results of the in silico investigation matched those of the in vivo study. Hence, Stevioside could be considered as a promising phytomedicine to treat T2DM.  相似文献   
83.
Aqueous two-phase systems consisting of dextran and polyethylene glycol (PEG) were used to study the partition behaviour of isoenzymes of lactate dehydrogenase (LDH; E.C. 1.1.1.27) from rabbit tissues in the presence and absence of a series of triazine dyes covalently coupled to PEG. The variations in the primary structures of LDH1(H4) and LDH5(M4) are reflected by significantly different partition coefficients. A class of dyes exhibiting defined structural elements is able to distinguish between both of these isoenzymes. This may be based on differences in the binding affinity to the catalytic site of the enzyme. The difference in the relative affinities of LDH1 and LDH5 to Procion Blue H-5R, as estimated by affinity partitioning, were corroborated by chromatographic experiments. Affinity partitioning in aqueous two-phase systems can be used to predict and to optimize conditions for the fast and simple chromatographic separation of isoenzymes.  相似文献   
84.
We consider a finite-population queueing system with heterogeneous classes of customers and a single server. For the case of nonpreemptive service, we fully characterize the structure of the server's optimal service policy that minimizes the total average customer waiting costs. We show that the optimal service policy may never serve some classes of customers. For those classes that are served, we show that the optimal service policy is a simple static priority policy. We also derive sufficient conditions that determine the optimal priority sequence.  相似文献   
85.
Water-soluble carboxylic acid derivatives of [60]fullerene retaining the original 60π electronic configuration are prepared from a tetra-tert-butyl ester of bis(fulleroid).  相似文献   
86.
87.
Cr-doped ZnS nanoparticles with Cr concentrations of 0.5, 1, 2 and 3 atm.% were successfully synthesized by the chemical co-precipitation method using ethylenediaminetetraacetic acid (EDTA) as the capping agent. The structural, optical and magnetic properties of the prepared samples were studied. Energy dispersive spectroscopy (EDS) measurements showed the presence of Cr in the Cr-doped ZnS. No mixed phase was observed from X-ray diffraction (XRD) studies and all the peaks were indexed to the cubic phase of ZnS. The average diameter of the particles was in the range of 6–10 nm, and it was confirmed by TEM studies. The magnetic behavior of the nanoparticles for different chromium concentrations was investigated by magnetism measurements using a vibrating sample magnetometer (VSM). The nanoparticles with lower Cr concentration exhibited strong ferromagnetism, where as in samples of higher Cr concentrations the ferromagnetism suppressed. The electron paramagnetic resonance (EPR) spectra of the nanocrystals showed the resonance of electron centers with a g-value of 1.989. The signal intensity and linewidth of the EPR signal increased with increasing Cr content. FTIR studies indicated that the nanoparticles were sterically stabilized by EDTA.  相似文献   
88.
89.
Theσ-charges on various atoms in inositols have been computed by using the MO-LCAO method of Del Re. The potential and free energies of seven inositols in the normal (N) and alternative (A) conformations have also been calculated. Minimization of the energies of these conformations have been studied by suitably tilting the axial hydroxyl groups. Tilts of about 1.5° are predicted for the hydroxyl groups involved in syn-axial interactions, in the minimum energy conformations. As in aldopyranoses, in inositols also conformations which have fewer axial hydroxyl groups are favoured. The present calculations predict the order of preference ofneo-, allo- andmuco-inositols in the equilibrium mixture, in accordance with the experimental results.  相似文献   
90.
In a recombinant antibody scFv format, the presence of an unpaired cysteine (Cys) is implicated in reduced soluble expression and inefficient presentation in phage display. Compared to other species, antibodies derived from rabbits are more likely to contain this unpaired Cys residue at position 80 (Cys80), when generated in a scFv format. In a screening campaign to isolate rabbit scFv against cardiac troponin I (cTnI), it was found that, a large proportion of isolated cTnI-specific clones contained unpaired Cys80. To analyze the factors that led to the selection of anti-cTnI Cys80 scFv, after five rounds of biopanning, the biopanning experiments were repeated with a Cys80 scFv (MG4Cys), its alanine variant (MG4Ala), and an irrelevant high expressing scFv control. It was found that the selection and subsequent enrichment of MG4Cys scFv was ousted by the superior expressing variant MG4Ala, indicating that the Cys80 scFv was selected primarily due to its affinity. It is evident that phage-based selection is influenced by specific sequence characteristics affecting the expression as well as the binding specificity and this needs to be taken into account for selection of optimal antibody derivatives.  相似文献   
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