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151.
Exposure of cells to chemotherapeutic drug doxorubicin, a DNA-damaging agent, induces an increase in the levels and activity of the wild-type p53 protein. Less well appreciated was the effect of cAMP levels on posttranslational modifications of p53 in response to doxorubicin. Here we show that elevation of cAMP in pre-B acute lymphoblastic leukemia NALM-6 cells significantly attenuated phosphorylation state of p53 at Ser6, Ser9, Ser15, Ser20, Ser37, Ser46 and Ser392 upon exposure to doxorubicin. Increased cAMP levels also shifted the ratio of the death promoter to death repressor genes via alteration of Bcl-2 and Bax proteins expression. In conclusion, our results suggest that activation of cAMP-signaling system may repress p53-dependent apoptosis in malignant cells exposed to doxorubicin.  相似文献   
152.
Fusarium spp. are ubiquitous fungi found in soil worldwide as both pathogenic and nonpathogenic strains. The signals leading to disease or the absence of disease are poorly understood. We recently showed that fusaric acid (FA), a nonspecific toxin produced by most Fusarium spp., could elicit various plant defense responses at 100 nM without toxic effect. In this study, we checked for the effect of FA on root and root hairs, probable first site of contact between the fungi and the host. Large FA concentrations reduce root and root-hair growth and induce a rapid transient membrane hyperpolarization, followed by a large depolarization, due to the inhibition of H(+)-ATPase currents. Nanomolar concentrations of FA induced only an early transient membrane hyperpolarization of root hairs compatible with the induction of a signal transduction pathway. FA at 10(-7) M failed to induce salicylic acid- and jasmonic acid/ethylene-dependent defense-related genes but inhibited the germination of the angiosperm parasite Orobanche ramosa in contact of FA-pretreated Arabidopsis thaliana seedlings. These data suggest that FA at nontoxic concentrations could activate signal transduction components necessary for plant-defense responses that could contribute to biocontrol activity of Fusarium spp.  相似文献   
153.
In the present article, we have presented the peristaltic flow of an Oldroyd 8-constant fluid in an endoscope. The governing equations for the flow problem are simplified using long wavelength and low Reynold's number approximations. The solutions of the simplified problem are calculated using (i) Homotopy analysis method and (ii) Shooting method. The comparison of both the solutions shows a very good agreement between the results. The graphical results for the velocity field and stresses are presented to show the physical behaviour of all the parameters appearing in the problem.  相似文献   
154.
Rat heart mitochondria became permeabilized to sucrose when incubated with 100 nmol of Ca2+/mg of protein in the presence of Pi. Ca2+ chelation with EGTA restored impermeability to sucrose, which became entrapped in the matrix space. t-Butylhydroperoxide markedly promoted permeabilization in the presence of Ca2+ but not in its absence, and Ca2+-plus-t-butylhydroperoxide-induced permeabilization was reversed by EGTA. The data suggest that Ca2+ and oxidative stress synergistically promote the reversible opening of an inner membrane pore.  相似文献   
155.
A phytochemical investigation on the ethyl acetate soluble fraction of Lonicera quinquelocularis (whole plant) led to the first time isolation of one new phthalate; bis(7-acetoxy-2-ethyl-5-methylheptyl) phthalate (3) and two new benzoates; neopentyl-4-ethoxy-3, 5-bis (3-methyl-2-butenyl benzoate (4) and neopentyl-4-hydroxy-3, 5-bis (3-methyl-2-butenyl benzoate (5) along with two known compounds bis (2-ethylhexyl phthalate (1) and dioctyl phthalate (2). Their structures were established on the basis of spectroscopic analysis and by comparison with available data in the literature. All the compounds (1–5) were tested for their acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activities in dose dependent manner. The IC50 (50% inhibitory effect) values of compounds 3 and 5 against AChE were 1.65 and 3.43 µM while the values obtained against BChE were 5.98 and 9.84 µM respectively. Compounds 2 and 4 showed weak inhibition profile.  相似文献   
156.
Manual offline analysis, of a scanning electron microscopy (SEM) image, is a time consuming process and requires continuous human intervention and efforts. This paper presents an image processing based method for automated offline analyses of SEM images. To this end, our strategy relies on a two-stage process, viz. texture analysis and quantification. The method involves a preprocessing step, aimed at the noise removal, in order to avoid false edges. For texture analysis, the proposed method employs a state of the art Curvelet transform followed by segmentation through a combination of entropy filtering, thresholding and mathematical morphology (MM). The quantification is carried out by the application of a box-counting algorithm, for fractal dimension (FD) calculations, with the ultimate goal of measuring the parameters, like surface area and perimeter. The perimeter is estimated indirectly by counting the boundary boxes of the filled shapes. The proposed method, when applied to a representative set of SEM images, not only showed better results in image segmentation but also exhibited a good accuracy in the calculation of surface area and perimeter. The proposed method outperforms the well-known Watershed segmentation algorithm.  相似文献   
157.
158.
Cln3(Δex7/8) mice harbor the most common genetic defect causing juvenile neuronal ceroid lipofuscinosis (JNCL), an autosomal recessive disease involving seizures, visual, motor and cognitive decline, and premature death. Here, to more thoroughly investigate the manifestations of the common JNCL mutation, we performed a broad phenotyping study of Cln3(Δex7/8) mice. Homozygous Cln3(Δex7/8) mice, congenic on a C57BL/6N background, displayed subtle deficits in sensory and motor tasks at 10-14 weeks of age. Homozygous Cln3(Δex7/8) mice also displayed electroretinographic changes reflecting cone function deficits past 5 months of age and a progressive decline of retinal post-receptoral function. Metabolic analysis revealed increases in rectal body temperature and minimum oxygen consumption in 12-13 week old homozygous Cln3(Δex7/8) mice, which were also seen to a lesser extent in heterozygous Cln3(Δex7/8) mice. Heart weight was slightly increased at 20 weeks of age, but no significant differences were observed in cardiac function in young adults. In a comprehensive blood analysis at 15-16 weeks of age, serum ferritin concentrations, mean corpuscular volume of red blood cells (MCV), and reticulocyte counts were reproducibly increased in homozygous Cln3(Δ) (ex7/8) mice, and male homozygotes had a relative T-cell deficiency, suggesting alterations in hematopoiesis. Finally, consistent with findings in JNCL patients, vacuolated peripheral blood lymphocytes were observed in homozygous Cln3(Δ) (ex7/8) neonates, and to a greater extent in older animals. Early onset, severe vacuolation in clear cells of the epididymis of male homozygous Cln3(Δ) (ex7/8) mice was also observed. These data highlight additional organ systems in which to study CLN3 function, and early phenotypes have been established in homozygous Cln3(Δ) (ex7/8) mice that merit further study for JNCL biomarker development.  相似文献   
159.
The serine protease granzyme B (GrB) plays an important role in the immune defense mediated by cytotoxic lymphocytes. Recombinant derivatives of this pro-apoptotic protein fused to tumor-targeting ligands hold promise for cancer therapy, but their applicability may be limited by promiscuous binding to nontarget tissues via electrostatic interactions. Here, we investigated cell binding and specific cytotoxicity of chimeric molecules consisting of wild-type or surface-charge-modified human GrB and the natural EGFR ligand TGFα for tumor targeting. We mutated two cationic heparin-binding motifs responsible for electrostatic interactions of GrB with cell surface structures, and genetically fused the resulting GrBcs derivative to TGFα for expression in the yeast Pichia pastoris . Purified GrBcs-TGFα (GrBcs-T) and a corresponding fusion protein employing wild-type GrB (GrB-T) displayed similar enzymatic activity and targeted cytotoxicity against EGFR-overexpressing breast carcinoma cells in the presence of an endosomolytic reagent. However, unspecific binding of the modified GrBcs-T variant to EGFR-negative cells was dramatically reduced, preventing the sequestration by nontarget cells in mixed cell cultures and increasing tumor-cell specificity. Likewise, modification of the GrB domain alleviated unspecific extracellular effects such as cell detachment indicative of extracellular matrix degradation. Our data demonstrate improved selectivity and functionality of surface-charge-modified GrBcs, suggesting this strategy as a general approach for the development of optimized GrB fusion proteins for therapeutic applications.  相似文献   
160.
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