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81.
    
An obstacle to effective uniform treatment of glioblastoma, especially at recurrence, is genetic and cellular intertumoral heterogeneity. Hence, personalized strategies are necessary, as are means to stratify potential targeted therapies in a clinically relevant timeframe. Functional profiling of drug candidates against patient-derived glioblastoma organoids (PD-GBO) holds promise as an empirical method to preclinically discover potentially effective treatments of individual tumors. Here, we describe our establishment of a PD-GBO-based functional profiling platform and the results of its application to four patient tumors. We show that our PD-GBO model system preserves key features of individual patient glioblastomas in vivo. As proof of concept, we tested a panel of 41 FDA-approved drugs and were able to identify potential treatment options for three out of four patients; the turnaround from tumor resection to discovery of treatment option was 13, 14, and 15 days, respectively. These results demonstrate that this approach is a complement and, potentially, an alternative to current molecular profiling efforts in the pursuit of effective personalized treatment discovery in a clinically relevant time period. Furthermore, these results warrant the use of PD-GBO platforms for preclinical identification of new drugs against defined morphological glioblastoma features.  相似文献   
82.
    
The nuclearization and validation of a new positron annihilation lifetime spectroscopy (PALS) system was ideally used to investigate vacancy defects generated by α self-irradiation in the UO2 matrix of several plutonium-doped samples. The damage levels studied ranged from 0 to 0.3 dpa. This study validated the operational protocols for actinide-doped materials. A lattice lifetime of about 170–180 ps was determined for the undoped UO2 matrix, which is consistent with the values reported in the literature. Alpha self-irradiation damage systematically increases the mean positron lifetime, resulting in a difference of 133 ps for a damage level of 0.3 dpa. Even at low damage values, a positron trapping site appears that corresponds to point defects involving an uranium vacancy, with a specific lifetime of about 310 ps. When annealed at 1373 K, some of these defects coalesce to form larger extended defects. The initial results for actinide-doped UO2 also confirm the high sensitivity of PALS to the presence of vacancy defects even at low integrated α dose.  相似文献   
83.
This paper presents the development of V(z) inversion technique and its application to quantitative determination of interface adhesion by measuring interface tangential stiffness parameter KT. The measurement is performed in two steps on an air plasma sprayed bronze-aluminum alloy coating (on a steel substrate) having different adhesion levels: the determination of the coating elastic constants and the determination of the interface tangential stiffness KT are performed by optimizing the inverted angular-frequency reflectance function R(θ,f). The results obtained by the V(z) inversion are then compared to mechanical testing by interfacial indentation on the same sample. The same behavior (quality of interface adhesion) can be seen by both methods: the coating adhesion decreases as the interfacial stiffness parameter KT decreases.  相似文献   
84.
This paper presents an innovative two-processor computer architecture, developed for the data processing unit (DPU) of the Magnetospheric IMaging Instrument (MIMI), on-board the Cassini spacecraft mission to Saturn. The main advantages of this architecture are its high performance and reliability, and its intelligence. The high performance is justified by the following: 1) optimum combination of two powerful Harris RTX 2010 processors; 2) adoption of two independent main bus structures used for the communication of the processors with the various instrument interfaces and subsystems; 3) adoption of two additional local buses on each processor board used to speed the on-board operations of the processors; 4) high speed interprocessor communication port. The high reliability is justified by the following: 1) simplicity of hardware/software structures; 2) fault tolerance capabilities; 3) capability for on-flight hardware/software reconfiguration by ground command. Moreover, the on-board intelligence is justified by the following: 1) sophisticated fault protection, data handling, and instrument control software; 2) intelligent interfaces [implemented using held programmable gate arrays (FPGAs)]; 3) capability for autonomous on-flight hardware/software reconfiguration in case of an unrecoverable failure in one processor. The advantages of this architecture make it the best choice for the DPU of the complex, sophisticated scientific MIMI instrument, compared to the traditional master-slave (low reliability-single point failure) and common shared bus (low performance, hardware and software complexity) architectures  相似文献   
85.
The nucleotide sequence of a 31 352 bp fragment from chromosome II of Saccharomyces cerevisiae has been determined and analysed. The fragment originates from the right arm of chromosome II, located between the GAL7,10,1 and the PHO3,5 loci, at a distance of about 130 kb from the centromere. The sequence contains a tRNA tandem repeat and 17 open reading frames (ORFs) larger than 100 amino acids. One of them extends into adjacent DNA and is incomplete. The two tRNA genes, coding for a tRNAasp and a tRNAarg, and three of the ORFs, had been sequenced previously, i.e. HSP26, SEC18, and UBC4. Four other ORFs showed similarity with yeast genes; amino acid transporter genes, the RAD54, SNF2 and STH1 family, the SPS2 gene and the bromodomain of SPT7, respectively. Two showed homology with sequences from other organisms, i.e. with a Plasmodium falciparum gene encoding a surface antigen and with a gene from Saimirine herpes virus respectively. Three ORFs, YBR0726, YBR0735 and YBR0740 are completely contained in YBR0727, YBR0734 and YBR0739 respectively, and thus probably do not represent real genes. Two ORFs, YBR0727 and YBR0745 most likely contain an intron. The sequences have been deposited in the EMBL data library under Accession Number X76294.  相似文献   
86.
    
The accurate generation of soft shadows is a particularly computationally intensive task. In order to reduce rendering time, most real‐time and offline applications decorrelate the generation of shadows from the computation of lighting. In addition to such approximations, they generate shadows using some restrictive assumptions only correct in very specific cases, leading to penumbra over‐estimation or light‐leaking artifacts. In this paper we present an algorithm that produces soft shadows without exhibiting the previous drawbacks. Using a new efficient evaluation of the number of occluders between two points (i.e. the depth complexity) we either modulate direct lighting or numerically solve the rendering equation for direct illumination. Our approach approximates shadows cast by semi‐opaque occluders and naturally handles area lights with spatially varying luminance. Furthermore, depending on the desired performance and quality, the resulting shadows are either very close to, or as accurate as, a ray‐traced reference. As a result, the presented method is well suited to many domains, ranging from quality‐sensitive to performance‐critical applications.  相似文献   
87.
    
Bacteria form multicellular and resistant structures named biofilms. Biofilm formation starts with the attachment phase, and the molecular actors involved in this phase, except adhesins, are poorly characterized. There is growing evidence that phospholipids are more than simple structural bricks. They are involved in bacterial adaptive physiology, but little is known about their role in biofilm formation. Here, we report a mass spectrometry analysis of the phospholipid (PL) profile of several strains of Pseudomonas aeruginosa isolated from cystic fibrosis patients. The aim of our study was to evaluate a possible link between the PL profile of a strain and its attachment phenotype. Our results showed that PL profile is strongly strain-dependent. The PL profile of P. aeruginosa PAO1, a collection strain, was different from those of 10 clinical isolates characterized either by a very low or a very high attachment capacity. We observed also that the clinical strain’s PL profiles varied even more importantly between isolates. By comparing groups of strains having similar attachment capacities, we identified one PL, PE 18:1-18:1, as a potential molecular actor involved in attachment, the first step in biofilm formation. This PL represents a possible target in the fight against biofilms.  相似文献   
88.
Oxidation of stainless steel in PWR primary water at 325 °C was studied by investigating the influence of defects created at the alloy subsurface by proton irradiation before corrosion exposure. Corrosion experiments were conducted by sequentially exposing samples, with H 2 18 O used for the second exposure. The oxide layer, formed in these conditions was studied by SEM and TEM and could be divided in two parts: an external discontinuous layer composed of crystallites rich in iron and an internal continuous layer richer in chromium. Tracer experiments revealed that the growth of this protective scale was due to oxygen diffusion in the grain boundary of the oxide layer. Defects created by irradiation have an effect on the two oxide layers. They are a preferential nucleation site for the external layer and so increase the density of the crystallites. They also induce a slower diffusion of oxygen in the internal layer.  相似文献   
89.
This article proposes an innovative multichannel optically stimulated luminescence (OSL) dosemeter for on-line in vivo dose verification in radiation therapy. OSL fibre sensors incorporating small Al(2)O(3):C fibre crystals (TLD(500)) have been tested with an X-ray generator. A reproducible readout procedure should reduce the fading-induced uncertainty ( approximately - 1% per decade). OSL readouts are temperature-dependent [ approximately 0.3% K(-1) when OSL stimulation is performed at the same temperature as irradiation; approximately 0.16% K(-1) after thermalisation (20 degrees C)]. Sensor calibration and depth-dose measurements with electron beams have been performed with a Saturne 43 linear accelerator in reference conditions at CEA-LNHB (ionising radiation reference laboratory in France). Predosed OSL sensors show a good repeatability in multichannel operation and independence versus electron energy in the range (9, 18 MeV). The difference between absorbed doses measured by OSL and an ionisation chamber were within +/-0.9% (for a dose of about 1 Gy) despite a sublinear calibration curve.  相似文献   
90.
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