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1.
Doxorubicin increases endothelial permeability, hence increasing cardiomyocytes’ exposure to doxorubicin (DOX) and exposing myocytes to more immediate damage. Reactive oxygen species are major effector molecules of doxorubicin’s activity. Mangiferin (MGN) is a xanthone derivative that consists of C-glucosylxanthone with additional antioxidant properties. This particular study assessed the effects of MGN on DOX-induced cytotoxicity in human umbilical vein endothelial cells’ (HUVECs’) signaling networks. Mechanistically, MGN dramatically elevated Nrf2 expression at both the messenger RNA and protein levels through the upregulation of the PI3K/AKT pathway, leading to an increase in Nrf2-downstream genes. Cell apoptosis was assessed with a caspase-3 activity assay, transferase-mediated dUTP-fluorescein nick end labeling (TUNEL) staining was performed to assess DNA fragmentation, and protein expression was determined by Western blot analysis. DOX markedly increased the generation of reactive oxygen species, PARP, caspase-3, and TUNEL-positive cell numbers, but reduced the expression of Bcl-2 and antioxidants’ intracellular concentrations. These were effectively antagonized with MGN (20 μM), which led to HUVECs being protected against DOX-induced apoptosis, partly through the PI3K/AKT-mediated NRF2/HO-1 signaling pathway, which could theoretically protect the vessels from severe DOX toxicity.  相似文献   
2.
Adult neurogenesis is a highly regulated process during which new neurons are generated from neural stem cells in two discrete regions of the adult brain: the subventricular zone of the lateral ventricle and the subgranular zone of the dentate gyrus in the hippocampus. Defects of adult hippocampal neurogenesis have been linked to cognitive decline and dysfunction during natural aging and in neurodegenerative diseases, as well as psychological stress-induced mood disorders. Understanding the mechanisms and pathways that regulate adult neurogenesis is crucial to improving preventative measures and therapies for these conditions. Accumulating evidence shows that mitochondria directly regulate various steps and phases of adult neurogenesis. This review summarizes recent findings on how mitochondrial metabolism, dynamics, and reactive oxygen species control several aspects of adult neural stem cell function and their differentiation to newborn neurons. It also discusses the importance of autophagy for adult neurogenesis, and how mitochondrial and autophagic dysfunction may contribute to cognitive defects and stress-induced mood disorders by compromising adult neurogenesis. Finally, I suggest possible ways to target mitochondrial function as a strategy for stem cell-based interventions and treatments for cognitive and mood disorders.  相似文献   
3.
Idiosyncratic drug-induced liver injury (IDILI) remains a significant problem for patients and drug development. The idiosyncratic nature of IDILI makes mechanistic studies difficult, and little is known of its pathogenesis for certain. Circumstantial evidence suggests that most, but not all, IDILI is caused by reactive metabolites of drugs that are bioactivated by cytochromes P450 and other enzymes in the liver. Additionally, there is overwhelming evidence that most IDILI is mediated by the adaptive immune system; one example being the association of IDILI caused by specific drugs with specific human leukocyte antigen (HLA) haplotypes, and this may in part explain the idiosyncratic nature of these reactions. The T cell receptor repertoire likely also contributes to the idiosyncratic nature. Although most of the liver injury is likely mediated by the adaptive immune system, specifically cytotoxic CD8+ T cells, adaptive immune activation first requires an innate immune response to activate antigen presenting cells and produce cytokines required for T cell proliferation. This innate response is likely caused by either a reactive metabolite or some form of cell stress that is clinically silent but not idiosyncratic. If this is true it would make it possible to study the early steps in the immune response that in some patients can lead to IDILI. Other hypotheses have been proposed, such as mitochondrial injury, inhibition of the bile salt export pump, unfolded protein response, and oxidative stress although, in most cases, it is likely that they are also involved in the initiation of an immune response rather than representing a completely separate mechanism. Using the clinical manifestations of liver injury from a number of examples of IDILI-associated drugs, this review aims to summarize and illustrate these mechanistic hypotheses.  相似文献   
4.
Immunotherapy is an efficient approach to clinical oncology. However, the immune privilege of the central nervous system (CNS) limits the application of immunotherapeutic strategies for brain cancers, especially glioblastoma (GBM). Tumor resistance to immune checkpoint inhibitors is a further challenge in immunotherapies. To overcome the immunological tolerance of brain tumors, a novel multifunctional nanoparticle (NP) for highly efficient synergetic immunotherapy is reported. The NP contains an anti-PDL1 antibody (aPDL1), upconverting NPs, and the photosensitizer 5-ALA; the surface of the NP is conjugated with the B1R kinin ligand to facilitate transport across the blood-tumor-barrier. Upon irradiation with a 980 nm laser, 5-ALA is transformed into protoporphyrin IX, generating reactive oxygen species. Photodynamic therapy (PDT) further promotes intratumoral infiltration of cytotoxic T lymphocytes and sensitizes tumors to PDL1 blockade therapy. It is demonstrated that combining PDT and aPDL1 can effectively suppress GBM growth in mouse models. The proposed NPs provide a novel and effective strategy for boosting anti-GBM photoimmunotherapy.  相似文献   
5.
《Ceramics International》2022,48(12):16839-16844
In this work, the effects of starting oxide powders with different-scale particle sizes on the synthesis of gadolinium zirconate pyrochlore (Gd2Zr2O7, GZO) and its physical properties were studied. Micron Gd2O3 (μG), micron ZrO2 (μZ), nano Gd2O3 (nG), and nano ZrO2 (nZ) powders were used. GZO ceramics were prepared by employing solid-state reactive sintering at 1300 °C, 1400 °C, 1500 °C and 1600 °C with mixed powders of different sizes (μGμZ, μGnZ, nGμZ and nGnZ). X-ray diffraction and Raman analyses of the ceramics revealed that nG has a more significant impact on the crystallization process than nZ. All ceramics synthesized with different sized oxide powders crystallized into pyrochlore phases except for those synthesized with μGnZ mixed powders, which resulted in a fluorite phase. The results indicated that decreasing the particle size of only ZrO2 to synthesize pyrochlore-phase Gd2Zr2O7 with high crystallinity may not be effective. Samples obtained at 1500 °C were further analyzed. Scanning electron microscopy results revealed that all four ceramics have a non-homogeneous grain size and that the average grain size ranges from 5.40 to 8.30 μm. In addition, the density and Vickers hardness measurements showed that the use of nanopowders significantly improves the mechanical properties.  相似文献   
6.
高红强 《染整技术》2020,42(1):38-40
活性染料具有良好的耐湿摩擦色牢度和匀染性,但也存在一些不足,如对温度、碱剂的敏感性较大,染色重现性差,固色率相对较低,色牢度不佳等。通过实验阐释电导率在活性染棉大货重现性上的应用,规避可预见性问题,寻找达到染色最佳效果的途径。  相似文献   
7.
8.
This paper presents parallel multipopulation differential evolutionary particle swarm optimization (DEEPSO) for voltage and reactive power control (VQC). The problem can be formulated as a mixed integer nonlinear optimization problem and various evolutionary computation techniques have been applied to the problem including PSO, differential evolution (DE), and DEEPSO. Since VQC is one of the online controls, speed‐up of computation is required. Moreover, there is still room for improvement in solution quality. This paper applies parallel multipopulation DEEPSO in order to speed up the calculation and improve solution quality. The proposed method is applied to IEEE 30, 57, and 118 bus systems. The results indicate that the proposed method can realize fast computation and minimize more active power losses than the conventional evolutionary computation techniques.  相似文献   
9.
The aim of this study is to reduce the phosphate concentration in treated wastewater using a small amount of the reactive filter media, Filtralite P. Biologically treated wastewater was passed through a filter with 215 g of Filtralite P. In the laboratory, the phosphate removal efficiency was 51% at a flow speed of 0.87 m/h. Under real conditions, in an experimental stand filled with 0.5 m3 of Filtralite P, the phosphate removal efficiency was 85% and the removal efficiency of total suspended solids was 57% after a 5‐month period. The residual phosphate concentration in the filtrate from the experimental stand was 1 mg/L of PO4‐P after the 5‐month period. The experimental filtration plant was buried in the ground, and it did not freeze and worked well under winter conditions. The results of this study can be useful in the design and development of tertiary wastewater treatment plants in view of their sustainability potential.  相似文献   
10.
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