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11.
Biliary tract cancers (BTC) represent a heterogeneous and aggressive group of tumors with dismal prognosis. For a long time, BTC has been considered an orphan disease with very limited therapeutic options. In recent years a better understanding of the complex molecular landscape of biology is rapidly changing the therapeutic armamentarium. However, while 40–50% of patients there are molecular drivers susceptible to target therapy, for the remaining population new therapeutic options represent an unsatisfied clinical need. The role of immunotherapy in the continuum of treatment of patients with BTC is still debated. Despite initial signs of antitumor-activity, single-agent immune checkpoint inhibitors (ICIs) demonstrated limited efficacy in an unselected population. Therefore, identifying the best partner to combine ICIs and predictive biomarkers represents a key challenge to optimize the efficacy of immunotherapy. This review provides a critical analysis of completed trials, with an eye on future perspectives and possible biomarkers of response.  相似文献   
12.
Platinum(II) complexes of the type [Pt(Cl)(PPh3){(κ2-N,O)-(1{C(R)=N(OH)-2(O)C6H4})}] with R=Me, H, ( 1 and 2 ) were synthesized and characterized. Single-crystal X-ray diffraction confirmed the proposed (SP4-3) configuration for 1 . Study of the antiproliferative activity, performed on a panel of human tumor cell lines and on mesothelial cells, highlighted complex 2 as the more effective. In particular, it showed a remarkable cytotoxicity in ovarian carcinoma cells (A2780) and interestingly, a significant antiproliferative effect on cisplatin resistant cells (A2780cis). Investigation into the intracellular mechanism of action demonstrated that 2 had a lower ability to platinate DNA than did cisplatin, which was taken as reference, and a notably higher uptake in resistant cells. A significant accumulation in mitochondria, along with the ability to induce concentration-dependent mitochondrial membrane depolarization and intracellular reactive oxygen species production, allowed us to propose a mitochondrion-mediated pathway as responsible for the interesting cytotoxic profile of complex 2 .  相似文献   
13.
14.
A characterisation of three commonly used impellers was made in this study by measuring local mean velocities and the fluctuations of these velocities with the LDV technique. The data was used to estimate volumetric flow, velocity fluctuations and turbulent intensity in the impeller region of the tank. The impellers investigated were a high flow impeller, a pitched blade turbine and a Rushton turbine. The cylindrical vessel used was made of Perspex, had a dished bottom (DIN 28013), was equipped with four baffles and had an inner diameter of 0.45 m. It was found that the bulk velocities could be scaled with the tip-speed of the impeller (ND). The flow rate at constant impeller speed increased in the order high flow impeller — Rushton turbine — pitched blade turbine. The corresponding order for the turbulence fluctuation is: high flow impeller — pitched blade turbine — Rushton turbine. The velocity profile of the flow out from the high flow impeller was furthermore, not as smooth as could be expected.  相似文献   
15.
Diffusion Tensor Imaging (DTI) is used to characterize the diffusion properties of deviated white matter caused by brain tumors. DTI was recently shown to be very helpful in delineating white matter both within brain lesions and surrounding them. Displacement of white matter fibers may be one of the consequences of tumor growth adjacent to white matter. The combination of white matter mapping with DTI and gray matter mapping using functional MRI, in some cases, facilitated assessment of the relation between the shifted cortical areas and the corresponding white matter tracts. We found that the fractional anisotropy extracted from DTI is increased by 38% in areas of non-edematous shifted white matter fibers. By contrast, trace apparent diffusion coefficient (ADC) values in those areas were found to be similar to contralateral side and normal control values. Analysis of the three diffusion tensor eigenvalues revealed that the increase in the fractional anisotropy is a result of two processes. The first is the increase in the diffusion parallel to the fibers—λ1 (by 18%), and the second is the decrease in the diffusion perpendicular to fibers—λ3 (by 34%) as compared with the contralateral side. These opposing changes cause an increase in the diffusion anisotropy but no change in the trace ADC. It is suggested that the pressure caused by the tumor may lead to an increase in white matter fiber tension, thus causing an increase in λ1. On the other hand, the same pressure causes increased fiber density per unit area, leading to a higher degree of restricted diffusion in the extracellular space and, hence, a reduction in λ3.  相似文献   
16.
When single-cell (or suspended) bacteria switch into the biofilm lifestyle, they become less susceptible to antimicrobials, imposing the need for anti-biofilms research. Flavonoids are among the most extensively studied natural compounds with an unprecedented amount of bioactivity claims. Most studies focus on the antibacterial effects against suspended cells; fewer reports have researched their anti-biofilm properties. Here, a high throughput phenotypic platform was utilized to screen for the inhibitory activity of 500 flavonoids, including natural and synthetic derivatives, against Staphylococcus aureus biofilms. Since discrepancies among results from earlier antibacterial studies on flavonoids had been noted, the current study aimed to minimize sources of variations. After the first screen, flavonoids were classified as inactive (443), moderately active (47) or highly active (10). Further, exclusion criteria combining bioactivity and selectivity identified two synthetic flavans as the most promising. The body of data reported here serves three main purposes. First, it offers an improved methodological workflow for anti-biofilm screens of chemical libraries taking into account the (many times ignored) connections between anti-biofilm and antibacterial properties. This is particularly relevant for the study of flavonoids and other natural products. Second, it provides a large and freely available anti-biofilm bioactivity dataset that expands the knowledge on flavonoids and paves the way for future structure-activity relationship studies and structural optimizations. Finally, it identifies two new flavans that can successfully act on biofilms, as well as on suspended bacteria and represent more feasible antibacterial candidates.  相似文献   
17.
In this study, we present a correlative microscopy workflow to combine detailed 3D fluorescence light microscopy data with ultrastructural information gained by 3D focused ion beam assisted scanning electron microscopy. The workflow is based on an optimized high pressure freezing/freeze substitution protocol that preserves good ultrastructural detail along with retaining the fluorescence signal in the resin embedded specimens. Consequently, cellular structures of interest can readily be identified and imaged by state of the art 3D confocal fluorescence microscopy and are precisely referenced with respect to an imprinted coordinate system on the surface of the resin block. This allows precise guidance of the focused ion beam assisted scanning electron microscopy and limits the volume to be imaged to the structure of interest. This, in turn, minimizes the total acquisition time necessary to conduct the time consuming ultrastructural scanning electron microscope imaging while eliminating the risk to miss parts of the target structure. We illustrate the value of this workflow for targeting virus compartments, which are formed in HIV‐pulsed mature human dendritic cells.  相似文献   
18.
We have studied the wavelength dependence of the two‐photon excitation efficiency for a number of common UV excitable fluorescent dyes; the nuclear stains DAPI, Hoechst and SYTOX Green, chitin‐ and cellulose‐staining dye Calcofluor White and Alexa Fluor 350, in the visible and near‐infrared wavelength range (540–800 nm). For several of the dyes, we observe a substantial increase in the fluorescence emission intensity for shorter excitation wavelengths than the 680 nm which is the shortest wavelength usually available for two‐photon microscopy. We also find that although the rate of photo‐bleaching increases at shorter wavelengths, it is still possible to acquire many images with higher fluorescence intensity. This is particularly useful for applications where the aim is to image the structure, rather than monitoring changes in emission intensity over extended periods of time. We measure the excitation spectrum when the dyes are used to stain biological specimens to get a more accurate representation of the spectrum of the dye in a cell environment as compared to solution‐based measurements.  相似文献   
19.
The effect of storage time and storage temperature on the formation of volatile compounds in dairy spreads was investigated. Dairy spreads were stored for 10 weeks at -18, 5 and 20 °C, respectively, and analyzed after 0, 38, 54 and 67 days of storage. By means of a dynamic headspace GC/MS method using Tenax traps the dairy spreads were analyzed for volatile aromatic compounds. 61 components were identified and their relative content was followed during the storage period. Among these were four alcohols, 17 aldehydes, four esters, ten alkanes, 11 ketones and six lactones. A general increase in the concentration of most of the volatile compounds during storage was found. The content of volatile compounds in dairy spreads stored at -18 °C was nearly constant or showed a rather low increase in the content during the storage period. Storage at higher temperatures (5 and 20 °C) resulted in an increase in the content of most of the volatiles after 40 days of storage. The profiles obtained were subjected to multivariate data analysis to determine the volatiles potentially responsible for oxidized off-flavors in dairy spread. The volatiles were divided into three groups: one correlated with storage temperature and 5 °C, one with storage time and 20 °C and the last with storage time alone. Most of the volatiles were found in the highest concentration after storage at 20 °C, but the content of some volatiles was highest after storage at 5 °C.  相似文献   
20.
In 1980, the CEC launched a call for tenders for photovoltaic pilot projects. Since mid 1984, all the relating plants are in operation. In late summer 198S, the WIP has been charged to inspect the PV plants, so as to gather information on the operational status of the systems.

This inspection showed that most of the plants are working satisfactorily. Nevertheless, optimization measures are possible for many installations in the field of power management and conditioning systems, data acquisition and recording, battery management and charge controlling, loads and load matching, software, maintenance and documentation.

So far, the PV modules themselves, the support structures and batteries have shown to be trouble-free components of PV systems.

In order to preserve the potential of the PV plants and make good use of it, the Commission sponsors, in the frame of the current photovoltaic R & D Programme, follow-up activities on the existing installations.  相似文献   
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