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581.
A Bayesian procedure for forecasting S‐shaped growth is introduced and compared to classical methods of estimation and prediction using three variants of the logistic functional form and annual times series of the diffusion of music compact discs in twelve countries. The Bayesian procedure was found not only to improve forecast accuracy, using the medians of the predictive densities as point forecasts, but also to produce intervals with a width and asymmetry more in accord with the outcomes than intervals from the classical alternative. While the analysis in this paper focuses on logistic growth, the problem is set up so that the methods are transportable to other characterizations of the growth process. Copyright © 2001 John Wiley & Sons, Ltd.  相似文献   
582.
A model previously developed by Lackman (C. L. Lackman, Forecasting commercial paper rates. Journal of Business Finance and Accounting 15 (1988) 499–524) for the period 1960 to 1985 is updated to include the 1990s and incorporate statistical techniques relating to tests for stationary conditions not available in 1988. As in the previous model, the demand for commercial paper by each institution (Households (HH), Life Insurance Companies (LIC), Non‐Financial Corporations (CRP) and Finance Corporations (FC)) and the total demand is simulated. Simulations of the commercial paper rate are also generated—using just the demand equations (total supply exogenous) and then employing the entire model (supply endogenous) to determine the rate. Simulation periods are from 1960:2 to 2001:4 for all demand simulations. The dynamic simulation of the total demand for commercial paper performs well. The resulting root mean square error, 3.485, compares favourably with the Federal Reserve Boston–Massachusetts Institute of Technology (FRB–MIT) estimate of the commercial paper rate (deLeeuw and Granlich, 1968). Copyright © 2004 John Wiley & Sons, Ltd.  相似文献   
583.
The most up‐to‐date annual average daily traffic (AADT) is always required for transport model development and calibration. However, the current‐year AADT data are not always available. The short‐term traffic flow forecasting models can be used to predict the traffic flows for the current year. In this paper, two non‐parametric models, non‐parametric regression (NPR) and Gaussian maximum likelihood (GML), are chosen for short‐term traffic forecasting based on historical data collected for the annual traffic census (ATC) in Hong Kong. These models are adapted as they are more flexible and efficient in forecasting the daily vehicular flows in the Hong Kong ATC core stations (in total of 87 stations). The daily vehicular flows predicted by these models are then used to calculate the AADT of the current year, 1999. The overall prediction and comparison results show that the NPR model produces better forecasts than the GML model using the ATC data in Hong Kong. Copyright © 2006 John Wiley _ Sons, Ltd.  相似文献   
584.
585.
This paper reports the degradation of indigo carmine and eosin Y dyes in water, catalyzed by cobalt and multiwalled carbon nanotube modified zirconium oxide nanocomposite(Co-ZrO_2-MWCNTs) under simulated visible light. The bare ZrO_2,ZrO_2-MWCNTs, Co-ZrO_2 and Co-ZrO_2-MWCNTs with different percentage compositions of cobalt were synthesized by homogeneous co-precipitation method. Characterization of the prepared nanocomposites was carried out using X-Ray powder Diffraction(XRD), Fourier Transformer Infrared(FTIR) Spectroscopy, Transmission Electron Microscopy(TEM), Raman Spectroscopy,(UV–Vis)-Spectroscopy and Energy Dispersive Spectroscopy(EDS) for their structure, formation,morphology, size and elemental analysis. The experimental results indicated that all the cobalt and MWCNTs modified nanocomposites demonstrated higher photocatalytic activities compared to the bare ZrO_2. The most efficient catalyst(0.5% Co-ZrO_2-MWCNTs) with the band gap and Ka values of 5.21 e V and 16.86*10~(-3) min~(-1) respectively exhibited 98% degradation efficiency toward indigo carmine and 87% toward eosin Y in 180 min.  相似文献   
586.
587.
DNA sequencing of a cytogenetically normal acute myeloid leukaemia genome   总被引:1,自引:0,他引:1  
Acute myeloid leukaemia is a highly malignant haematopoietic tumour that affects about 13,000 adults in the United States each year. The treatment of this disease has changed little in the past two decades, because most of the genetic events that initiate the disease remain undiscovered. Whole-genome sequencing is now possible at a reasonable cost and timeframe to use this approach for the unbiased discovery of tumour-specific somatic mutations that alter the protein-coding genes. Here we present the results obtained from sequencing a typical acute myeloid leukaemia genome, and its matched normal counterpart obtained from the same patient's skin. We discovered ten genes with acquired mutations; two were previously described mutations that are thought to contribute to tumour progression, and eight were new mutations present in virtually all tumour cells at presentation and relapse, the function of which is not yet known. Our study establishes whole-genome sequencing as an unbiased method for discovering cancer-initiating mutations in previously unidentified genes that may respond to targeted therapies.  相似文献   
588.
Activating mutations in ALK provide a therapeutic target in neuroblastoma   总被引:1,自引:0,他引:1  
Neuroblastoma, an embryonal tumour of the peripheral sympathetic nervous system, accounts for approximately 15% of all deaths due to childhood cancer. High-risk neuroblastomas are rapidly progressive; even with intensive myeloablative chemotherapy, relapse is common and almost uniformly fatal. Here we report the detection of previously unknown mutations in the ALK gene, which encodes a receptor tyrosine kinase, in 8% of primary neuroblastomas. Five non-synonymous sequence variations were identified in the kinase domain of ALK, of which three were somatic and two were germ line. The most frequent mutation, F1174L, was also identified in three different neuroblastoma cell lines. ALK complementary DNAs encoding the F1174L and R1275Q variants, but not the wild-type ALK cDNA, transformed interleukin-3-dependent murine haematopoietic Ba/F3 cells to cytokine-independent growth. Ba/F3 cells expressing these mutations were sensitive to the small-molecule inhibitor of ALK, TAE684 (ref. 4). Furthermore, two human neuroblastoma cell lines harbouring the F1174L mutation were also sensitive to the inhibitor. Cytotoxicity was associated with increased amounts of apoptosis as measured by TdT-mediated dUTP nick end labelling (TUNEL). Short hairpin RNA (shRNA)-mediated knockdown of ALK expression in neuroblastoma cell lines with the F1174L mutation also resulted in apoptosis and impaired cell proliferation. Thus, activating alleles of the ALK receptor tyrosine kinase are present in primary neuroblastoma tumours and in established neuroblastoma cell lines, and confer sensitivity to ALK inhibition with small molecules, providing a molecular rationale for targeted therapy of this disease.  相似文献   
589.
The M2 protein from influenza A virus is a pH-activated proton channel that mediates acidification of the interior of viral particles entrapped in endosomes. M2 is the target of the anti-influenza drugs amantadine and rimantadine; recently, resistance to these drugs in humans, birds and pigs has reached more than 90% (ref. 1). Here we describe the crystal structure of the transmembrane-spanning region of the homotetrameric protein in the presence and absence of the channel-blocking drug amantadine. pH-dependent structural changes occur near a set of conserved His and Trp residues that are involved in proton gating. The drug-binding site is lined by residues that are mutated in amantadine-resistant viruses. Binding of amantadine physically occludes the pore, and might also perturb the pK(a) of the critical His residue. The structure provides a starting point for solving the problem of resistance to M2-channel blockers.  相似文献   
590.
Pre-existing neutralizing antibody provides the first line of defence against pathogens in general. For influenza virus, annual vaccinations are given to maintain protective levels of antibody against the currently circulating strains. Here we report that after booster vaccination there was a rapid and robust influenza-specific IgG+ antibody-secreting plasma cell (ASC) response that peaked at approximately day 7 and accounted for up to 6% of peripheral blood B cells. These ASCs could be distinguished from influenza-specific IgG+ memory B cells that peaked 14-21 days after vaccination and averaged 1% of all B cells. Importantly, as much as 80% of ASCs purified at the peak of the response were influenza specific. This ASC response was characterized by a highly restricted B-cell receptor (BCR) repertoire that in some donors was dominated by only a few B-cell clones. This pauci-clonal response, however, showed extensive intraclonal diversification from accumulated somatic mutations. We used the immunoglobulin variable regions isolated from sorted single ASCs to produce over 50 human monoclonal antibodies (mAbs) that bound to the three influenza vaccine strains with high affinity. This strategy demonstrates that we can generate multiple high-affinity mAbs from humans within a month after vaccination. The panel of influenza-virus-specific human mAbs allowed us to address the issue of original antigenic sin (OAS): the phenomenon where the induced antibody shows higher affinity to a previously encountered influenza virus strain compared with the virus strain present in the vaccine. However, we found that most of the influenza-virus-specific mAbs showed the highest affinity for the current vaccine strain. Thus, OAS does not seem to be a common occurrence in normal, healthy adults receiving influenza vaccination.  相似文献   
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