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101.
    
Hepatitis B virus (HBV) chronically infects more than 240 million people worldwide, causing chronic hepatitis, cirrhosis, and hepatocellular carcinoma (HCC). Genome editing using CRISPR/Cas9 could provide new therapies because it can directly disrupt HBV genomes. However, because HBV genome sequences are highly diverse, the identical target sequence of guide RNA (gRNA), 20 nucleotides in length, is not necessarily present intact in the target HBV DNA in heterogeneous patients. Consequently, possible genome-editing drugs would be effective only for limited numbers of patients. Here, we show that an adenovirus vector (AdV) bearing eight multiplex gRNA expression units could be constructed in one step and amplified to a level sufficient for in vivo study with lack of deletion. Using this AdV, HBV X gene integrated in HepG2 cell chromosome derived from a heterogeneous patient was cleaved at multiple sites and disrupted. Indeed, four targets out of eight could not be cleaved due to sequence mismatches, but the remaining four targets were cleaved, producing irreversible deletions. Accordingly, the diverse X gene was disrupted at more than 90% efficiency. AdV containing eight multiplex gRNA units not only offers multiple knockouts of genes, but could also solve the problems of heterogeneous targets and escape mutants in genome-editing therapy.  相似文献   
102.
    
A linear inertial electrostatic confinement fusion neutron source equipped with a cooling system for high power operation was developed and its discharge characteristics and neutron production performance were tested under a wide range of discharge conditions. Four different types of discharge anodes were prepared and the dependencies of the device performance on the anode shape were precisely investigated. A maximum neutron production rate of 3.4×106 n/s was achieved when the device was operated with single‐cylinder‐type anodes under a discharge voltage of 94 kV, a current of 20 mA, and a deuterium gas pressure of 0.5 Pa. By comparing the discharge characteristics and neutron generation rates under different anode shapes, we found that the larger inner diameter of the anode leads to longer effective gap length and lower operating pressure, which may result in relatively high fusion reaction rate observed with the single‐cylinder‐type anodes.  相似文献   
103.
    
The objectives of this study were to reconstruct the design process of the Japanese pavilion in Venice Biennale, Italy (1956) designed by Takamasa Yoshizaka and to reveal the architect's formal manipulations and underlying strategic design thinking. The study materials are the original design sketches held in the National Archives of Modern Architecture, Tokyo, Japan. Initially, the chronological order of the design sketches was established by inspecting their dates and analyzing their formal similarities. The transformability (variations or changes of architectural form presented in a certain state of design) was analyzed and interpreted through a series of “studies” (partial problem-solving processes). Finally, the architect's formal manipulations were reconstructed and presented and his relevant design intentions were revealed.  相似文献   
104.
    
DNA origami methods enable the fabrication of various nanostructures and nanodevices, but their effective use depends on an understanding of their structural and mechanical properties and the effects of basic structural features. Frequency‐modulation atomic force microscopy is introduced to directly characterize, in aqueous solution, the crossover regions of sets of 2D DNA origami based on different crossover/nick designs. Rhombic‐shaped nanostructures formed under the influence of flexible crossovers placed between DNA helices are observed in DNA origami incorporating crossovers every 3, 4, or 6 DNA turns. The bending rigidity of crossovers is determined to be only one‐third of that of the DNA helix, based on interhelical electrostatic forces reported elsewhere, and the measured pitches of the 3‐turn crossover design rhombic‐shaped nanostructures undergoing negligible bending. To evaluate the robustness of their structural integrity, they are intentionally and simultaneously stressed using force‐controlled atomic force microscopy. DNA crossovers are verified to have a stabilizing effect on the structural robustness, while the nicks have an opposite effect. The structural and mechanical properties of DNA origami and the effects of crossovers and nicks revealed in this paper can provide information essential for the design of versatile DNA origami structures that exhibit specified and desirable properties.  相似文献   
105.
The effect of ultraviolet light irradiation on the characteristics of the polyethylene (PE) surface was investigated by the quartz crystal microbalance (QCM) technique. The PE film was prepared on the gold electrodes of the QCM by spin-coating from the solution and then was treated by the excimer UV lamp in ambient air. The changes in the hydrophilic properties, moisture adsorption, and water retention of the PE film due to the UV irradiation were determined from the frequency change of the QCM. To evaluate the detergency of the PE film, stearic acid as model oily soil was deposited onto the PE film formed on the QCM by the Langmuir-Blodgett (LB) technique, and was ultrasonically cleaned in aqueous detergent solutions containing ethanol or surfactant. The removal efficiency obtained from the frequency change of the QCM was found to increase considerably after the UV irradiation. From independently determined contact angles and the surface free energy components of the PE film, the free energy change resulting from the penetration of the detergent solution between stearic acid and PE in the zone of contact was calculated. Good relation was found between the removal efficiency and the free energy change, indicating that the increase in the detergency of the PE surface by UV irradiation was explained by surface energetics.  相似文献   
106.
The adzuki bean borer, Ostrinia scapulalis, has distinct genetic variation in the blend of two sex pheromone components, (E)- and (Z)-11-tetradecenyl acetates. This variation is largely controlled by a single autosomal locus with two alleles, E and Z. E-type (EE) females produce a pheromone with a mean E:Z ratio at 99:1 whereas Z-type (ZZ) and I-type (ZE) produce pheromones with mean of 3:97 and 64:36, respectively. Interestingly, in many natural populations of O. scapulalis in Japan, this pheromone polymorphism appears to be stably maintained. We tried to predict the changes in relative abundance of each pheromone type by estimating the pheromone production genotype of wild females and their male mates. The pheromone titer in the wild, mated females was increased without changing the blend ratio by an injection of a peptide with pheromone biosynthesis activating activity (TKYFSPRL-NH2). The frequencies of E-, I-, and Z-types at Matsudo were 15, 52, and 33%, respectively, and did not deviate from the Hardy-Weinberg expectations. The estimated mating patterns were concordant with the assumption that no assortative mating was occurring in this population, and this is suggested as a cause of sustained polymorphism at Matsudo.  相似文献   
107.
    
Minimally invasive boron neutron capture therapy (BNCT) is an elegant approach for cancer treatment. The highly selective and efficient deliverability of boron agents to cancer cells is the key to maximizing the therapeutic benefits of BNCT. In addition, enhancement of the frequencies to achieve boron neutron capture reaction is also significant in improving therapeutic efficacy by providing a highly concentrated boron agent in each boron nanoparticle. As the density of the thermal neutron beam remains low, it is unable to induce high-efficiency cell destruction. Herein, we report phospholipid-coated boronic oxide nanoparticles as agents for BNCT that can provide a highly concentrated boron atom in each nanoparticle. The current system exhibited in vitro BNCT activity seven times higher than that of commercial boron agents. Furthermore, the system could penetrate cancer spheroids deeply, efficiently suppressing thermal neutron irradiation-induced growth.  相似文献   
108.
In the presence of hydroxylamine or ascorbic acid, the inhibitory effects of Cu2+ on lysosomal acid cholesteryl ester hydrolase (acid CEH) partially purified from rat liver were studied. Hydroxylamine stimulated the inhibition of acid CEH activity by Cu2+ but not that by Zn2+, Fe2+, Co2+, Mn2+, Ca2+, Mg2+ and Hg2+. This Cu2+-dependent inhibition of acid cholesterol ester hydrolase (CEH) activity was completely prevented by ethylenediamine tetraacetic acid (EDTA), EGTA and o-phenanthroline, a chelator with a stability constant for Cu2+, and also by sulfhydryl agents and cytoplasmic reducing agents such as cysteine, glutathione and mercaptoethanol. In addition, the stimulative effects of hydroxylamine on Cu2+-dependent inhibition were maintained even after preincubation of Cu2+ with hydroxylamine. On the other hand, ascorbic acid was found to replace the stimulation by hydroxylamine of the Cu2+-dependent inhibition of acid CEH activity but the effects of ascorbic acid progressively became smaller with prolongation of the preincubation time. Moreover, addition of chemical radical scavengers to the reaction mixture did not prevent the Cu2+-dependent inhibition of acid CEH activity in the presence of ascorbic acid. These results suggest that Cu2+ causes inhibition of lysosomal acid CEH activity through the formation of Cu1+ in a reductive medium.  相似文献   
109.
Grafting of N,N-dimethylacrylamide (DMAA) onto polytetrafluoroethylene (PTFE) has been carried out by using gamma rays from a 60Co source. Degree of grafting was affected by grafting conditions. Especially, solvent for the grafting was found to be a very significant parameter to obtain a higher grafting yield. When ethylacetate or acetone was used as the solvent, grafting yield greater than 5% was obtainable while the graftcopolymerization scarcely occurred in the presence of other kinds of solvent such as ethanol or water. Apparent activation energy of the grafting in ethylacetate was calculated to be 7.90 Kcal/mol, and initial grafting rate of it was proportional to 0.55 power of dose rate.  相似文献   
110.
A 56-year-old Japanese woman was referred to us for the treatment of lung cancer. On admission, the patient showed multiple bone metastases, including the skull, without brain metastasis. During chemoradiotherapy for the primary tumor and bone metastasis involving the thoracic spine, she suffered a fatal intracerebral hemorrhage. Since the patient had no risk factors for intracerebral hemorrhage, the skull bone metastasis was thought to be responsible for this event. At autopsy, penetration of the metastatic tumor from the skull bone into the dura, with direct invasion of the brain tissue, was confirmed histologically. A hematoma also was identified at the same site adjacent to the skull bone metastasis. To our knowledge, direct tumor invasion to the brain from a skull metastasis of non-small cell lung cancer has not been previously reported.  相似文献   
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