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81.
    
Paper-based microfluidics is characteristic of fluid transportation through spontaneous capillary action of paper and has exhibited great promise for a variety of applications especially for sensing. Furthermore, paper-based microfluidics enables the design of miniaturized electrochemical devices to be applied in the energy sector, which is especially attractive for the rapid growing market of small size disposable electronics. This review gives a brief summary on the basics of paper chemistry and capillary-driven microfluidic behavior, and highlights recent advances of paper-based microfluidics in developing electrochemical sensing devices and miniaturized energy storage/conversion devices. Their structural features, working principles and exemplary applications are comprehensively elaborated and discussed. Additionally, this review also points out the existing challenges and future opportunities of paper-based microfluidic electronics.  相似文献   
82.
    
Molecular photoswitches triggered with red or NIR light are optimal for photomodulation of complex biological systems, including efficient penetration of the human body for therapeutic purposes (“therapeutic window”). Yet, they are rarely reported, and even more rarely functional under aqueous conditions. In this work, fluorinated azobenzenes are shown to exhibit efficient E→Z photoisomerization with red light (PSS660nm >75 % Z) upon conjugation with unsaturated substituents. Initially demonstrated for aldehyde groups, this effect was also observed in a more complex structure by incorporating the chromophore into a cyclic dipeptide with propensity for self-assembly. Under physiological conditions, the latter molecule formed a supramolecular material that reversibly changed its viscosity upon irradiation with red light. Our observation can lead to design of new photopharmacology agents or phototriggered materials for in vivo use.  相似文献   
83.
    
Polymer-based protein engineering has enabled the synthesis of a variety of protein–polymer conjugates that are widely applicable in therapeutic, diagnostic and biotechnological industries. Accurate characterizations of physical–chemical properties, in particular, molar masses, sizes, composition and their dispersities are critical parameters that determine the functionality and conformation of protein–polymer conjugates and are important for creating reproducible manufacturing processes. Most of the current characterization techniques suffer from fundamental limitations and do not provide an accurate understanding of a sample''s true nature. In this paper, we demonstrate the advantage of asymmetrical flow field-flow fractionation (AF4) coupled with multiple detectors for the characterization of a library of complex, zwitterionic and neutral protein–polymer conjugates. This method allows for determination of intrinsic physical properties of protein–polymer chimeras from a single, rapid measurement.

Precise characterization of structural parameters and their polydispersities of protein–polymer conjugates is performed with rapid analysis using asymmetrical flow field-flow fractionation coupled with multiple detectors.  相似文献   
84.
    
Product identification tags are of great importance in a globalized world with increasingly complex trading routes and networks. Beyond currently used coding strategies, such as QR codes, higher data density, flexible application as well as miniaturization and readout indication are longed for in the next generation of security tags. In this work, micron-sized supraparticles (SPs) with encoded information (ID) are produced that not only exhibit multiple initially covert identification levels but are also irreversibly marked as “read” upon readout. To achieve this, lanthanide doped CaF2 nanoparticles are assembled in various quantity-weighted ratios via spray-drying in presence of a broad-spectrum stealth fluorophore (StFl), yielding covert spectrally encoded ID-SPs. Using these as pigments, QR codes, initially dominated by the green fluorescence of the StFl, could be generated. Upon thermal energy input, these particle-based tags irreversibly switch to an activated state revealing not only multiple luminescent colors but also spectral IDs. This strategy provides the next generation of material-based security tags with a high data density and security level that switch information upon readout and can be, therefore, used as seal of quality.  相似文献   
85.
    
TASK channels belong to the two-pore-domain potassium (K2P) channels subfamily. These channels modulate cellular excitability, input resistance, and response to synaptic stimulation. TASK-channel inhibition led to membrane depolarization. TASK-3 is expressed in different cancer cell types and neurons. Thus, the discovery of novel TASK-3 inhibitors makes these bioactive compounds very appealing to explore new cancer and neurological therapies. TASK-3 channel blockers are very limited to date, and only a few heterofused compounds have been reported in the literature. In this article, we combined a pharmacophore hypothesis with molecular docking to address for the first time the rational design, synthesis, and evaluation of 5-(indol-2-yl)pyrazolo[3,4-b]pyridines as a novel family of human TASK-3 channel blockers. Representative compounds of the synthesized library were assessed against TASK-3 using Fluorometric imaging plate reader—Membrane Potential assay (FMP). Inhibitory properties were validated using two-electrode voltage-clamp (TEVC) methods. We identified one active hit compound (MM-3b) with our systematic pipeline, exhibiting an IC50 ≈ 30 μM. Molecular docking models suggest that compound MM-3b binds to TASK-3 at the bottom of the selectivity filter in the central cavity, similar to other described TASK-3 blockers such as A1899 and PK-THPP. Our in silico and experimental studies provide a new tool to predict and design novel TASK-3 channel blockers.  相似文献   
86.
    
In a global context where trading of wines involves considerable economic value, the requirement to guarantee wine authenticity can never be underestimated. With the ever-increasing advancements in analytical platforms, research into spectroscopic methods is thriving as they offer a powerful tool for rapid wine authentication. In particular, spectroscopic techniques have been identified as a user-friendly and economical alternative to traditional analyses involving more complex instrumentation that may not readily be deployable in an industry setting. Chemometrics plays an indispensable role in the interpretation and modelling of spectral data and is frequently used in conjunction with spectroscopy for sample classification. Considering the variety of available techniques under the banner of spectroscopy, this review aims to provide an update on the most popular spectroscopic approaches and chemometric data analysis procedures that are applicable to wine authentication.  相似文献   
87.
    
FAH domain containing protein 1 (FAHD1) acts as oxaloacetate decarboxylase in mitochondria, contributing to the regulation of the tricarboxylic acid cycle. Guided by a high-resolution X-ray structure of FAHD1 liganded by oxalate, the enzymatic mechanism of substrate processing is analyzed in detail. Taking the chemical features of the FAHD1 substrate oxaloacetate into account, the potential inhibitor structures are deduced. The synthesis of drug-like scaffolds afforded first-generation FAHD1-inhibitors with activities in the low micromolar IC50 range. The investigations disclosed structures competing with the substrate for binding to the metal cofactor, as well as scaffolds, which may have a novel binding mode to FAHD1.  相似文献   
88.
    
Resveratrol, a natural plant phytoalexin, is produced in response to fungal infection or− UV irradiation. It exists as an isomeric pair with cis- and trans-conformation. Whereas multiple physiological effects of the trans-form, including a pronounced anti-tumoral activity, are nowadays elucidated, much less knowledge exists concerning the cis-isomer. In our work, we analyzed the antiproliferative and cytotoxic properties of cis-resveratrol in four different human tumor entities in direct comparison to trans-resveratrol. We used human cell lines as tumor models for hepatocellular carcinoma (HCC; HepG2, Hep3B), colon carcinoma (HCT-116, HCT-116/p53(−/−)), pancreatic carcinoma (Capan-2, MiaPaCa-2), and renal cell carcinoma (A498, SN12C). Increased cytotoxicity in all investigated tumor cells was observed for the trans-isomer. To verify possible effects of the tumor suppressor p53 on resveratrol-induced cell death, we used wild type and p53-deleted or -mutated cell lines for every tested tumor entity. Applying viability and cytotoxicity assays, we demonstrated a differential, dose-dependent sensitivity towards cis- or trans-resveratrol among the respective tumor types.  相似文献   
89.
    
In continuation of the search for new anthelmintic natural products, the study at hand investigated the nematicidal effects of the two naturally occurring quassinoids ailanthone and bruceine A against the reproductive system of the model nematode Caenorhabditis elegans to pinpoint their anthelmintic mode of action by the application of various microscopic techniques. Differential Interference Contrast (DIC) and the epifluorescence microscopy experiments used in the presented study indicated the genotoxic effects of the tested quassinoids (c ailanthone = 50 µM, c bruceine A = 100 µM) against the nuclei of the investigated gonadal and spermathecal tissues, leaving other morphological key features such as enterocytes or body wall muscle cells unimpaired. In order to gain nanoscopic insight into the morphology of the gonads as well as the considerably smaller spermathecae of C. elegans, an innovative protocol of polyethylene glycol embedding, ultra-sectioning, acridine orange staining, tissue identification by epifluorescence, and subsequent AFM-based ultrastructural data acquisition was applied. This sequence allowed the facile and fast assessment of the impact of quassinoid treatment not only on the gonadal but also on the considerably smaller spermathecal tissues of C. elegans. These first-time ultrastructural investigations on C. elegans gonads and spermathecae by AFM led to the identification of specific quassinoid-induced alterations to the nuclei of the reproductive tissues (e.g., highly condensed chromatin, impaired nuclear membrane morphology, as well as altered nucleolus morphology), altogether implying an apoptosis-like effect of ailanthone and bruceine A on the reproductive tissues of C. elegans.  相似文献   
90.
    
This paper extends the recently introduced assignment flow approach for supervised image labeling to unsupervised scenarios where no labels are given. The resulting self‐assignment flow takes a pairwise data affinity matrix as input data and maximizes the correlation with a low‐rank matrix that is parametrized by the variables of the assignment flow, which entails an assignment of the data to themselves through the formation of latent labels (feature prototypes). A single user parameter, the neighborhood size for the geometric regularization of assignments, drives the entire process. By smooth geodesic interpolation between different normalizations of self‐assignment matrices on the positive definite matrix manifold, a one‐parameter family of self‐assignment flows is defined. Accordingly, our approach can be characterized from different viewpoints, e.g. as performing spatially regularized, rank‐constrained discrete optimal transport, or as computing spatially regularized normalized spectral cuts. Regarding combinatorial optimization, our approach successfully determines completely positive factorizations of self‐assignments in large‐scale scenarios, subject to spatial regularization. Various experiments including the unsupervised learning of patch dictionaries using a locally invariant distance function, illustrate the properties of the approach.  相似文献   
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