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991.
The peroral administration of (poly)peptide drugs requires the development of delivery systems, which provide a protective effect toward a gastrointestinal enzymatic attack. A promising strategy for such systems represents polymer-enzyme inhibitor conjugates in which the embedded therapeutic agent is protected. However, the practical use of polymer-inhibitor conjugates has so far been limited by high production costs of these auxiliary agents. To solve this problem for delivery systems shielding from pepsinic degradation, structurally simplified analogues of the pepsin inhibitor pepstatin A have been synthesized. The synthesis of tripeptide analogues, described by McConnell et al., led us to pursue further modifications varying the C-terminus. Our target to attach a spacer moiety-enabling the free access of pepsin to the inhibitor-should be combined with an attractive synthetic approach providing low production costs in large-scale preparation. Structure modifications comprised either the side chain of the third amino acid which served as starting compound designing the C-terminus (L-leucine, L-isoleucine, L-norvaline) as the length of the spacer link, simulated by a linear alkyl group (n-butyl, n-hexyl, and n-octyl). The inhibitory activities which have been evaluated by an enzyme assay were significantly dependent on the nature of the side chain, whereas the length of the spacer had no influence on the inhibitory effect. Analogues bearing the isobutyl or n-propyl moiety as side chain displayed a strong inhibitory effect which was comparable to that pepstatin A. These congeners represent promising auxiliary agents for the peroral administration of (poly)peptide drugs. 相似文献
992.
A Seven Y Erbil R Seven F Inci T Gülya?ar B Barut?u G Candan 《Canadian Metallurgical Quarterly》1998,16(4):333-345
The 'WHO Analgesic Ladder' is a well validated approach for the selection of appropriate analgesic therapy for cancer pain as well as pain in AIDS. The mainstay of analgesic intervention for cancer and AIDS pain of moderate to severe intensity continues to be the appropriate use of opioid analgesics. There is, however, a growing appreciation for the role of adjuvant analgesics, such as antidepressants and other psychotropic medications, at each step of the WHO Analgesic Ladder, particularly in the treatment of neuropathic pain. Knowledge of the indications and usefulness of psychotropic analgesic drugs in cancer and AIDS pain populations will be most important to clinicians practicing in psycho-oncology/AIDS settings, particularly since these drugs are useful not only in the treatment of psychiatric complications of cancer and AIDS, but also as adjuvant analgesic agents in the management of pain. This paper reviews the literature on the use of antidepressants, psychostimulants, neuroleptics, anticonvulsants and other psychotropic analgesics in the management of cancer and AIDS pain. Mechanisms of analgesia, drug selection, and recommendations for clinical usage are discussed. The appropriate and timely use of psychotropic adjuvant analgesic drugs represents an opportunity for active psychiatric contribution to the multidisciplinary management of cancer and AIDS pain. 相似文献
993.
This report describes a simple, rapid, automated microassay for measuring in vitro changes of oxidative burst of phagocytes following challenge with metals for orthopedic devices. The production of reactive oxygen species (ROS) by polymorphonuclear leukocytes (PMNs) was measured using 2',7'-dichlorofluorescin-diacetate (DCFH-DA) as fluorescent probe. DCFH-DA enters the cells and is oxidized by ROS to fluorescent DCF. The DCF generated was directly proportional to ROS produced intracellularly: The fluorescence intensity was read and converted to an index of ROS production by cells. In our experimental system, granulocytes (PMNs) were isolated from normal human blood and seeded in microplates. To verify if metals could influence ROS production, chromium, cobalt, nickel, molybdenum, titanium, aluminum, and vanadium prepared as aqueous extracts in phosphate-buffered saline were tested onto PMNs using phorbolmyristate acetate (PMA) as positive control. Molybdenum, aluminum, and vanadium increased ROS generation by PMNs, while signals not different from unstimulated PMNs were recorded for chromium, cobalt, nickel, and titanium. The DCFH-DA microplate-based assay provides an in vitro tool for the detection of oxygen-reactive species generated by PMNs as a response to metals. 相似文献
994.
A Blume K Seifert CJ Lebrun E M?llenhoff P Gass T Unger T Herdegen 《Canadian Metallurgical Quarterly》1998,241(2-3):87-90
Binding to olfactory receptors is the first step in odorant and pheromonal recognition and discrimination. These receptors constitute one of the most important, although poorly known, families of neuronal receptors. In this study we used degenerated oligonucleotides and a RT-PCR approach to selectively amplify olfactory receptors in the nasal epithelium of the domestic pig Sus scrofa. Several combinations of oligonucleotide were tested and allowed the isolation of eleven different partial sequences belonging to the seven transmembrane olfactory receptor family. These receptors formed a separate family within the seven transmembrane receptor superfamily in pigs. Using the criteria of Ben Arie et al. [Ben-Arie N., Lancet D., Taylor C., Khen M., Walker N., Ledbetter DH., Carrozzo R., Patel K., Sheer D., Lehrah H. and North M., Hum. Mol. Genet., 3 (1994) 229-235], the 11 receptors described here can be classified into three known families and seven subfamilies (one known and six new). 相似文献
995.
We investigated the effect of changes in membrane-voltage on intracellular sodium concentration ([Na+]i) of dopamine-sensitive neurons of the substantia nigra pars compacta in a slice preparation of rat mesencephalon. Whole-cell patch-clamp techniques were combined with microfluorometric measurements of [Na+]i using the Na+-sensitive probe, sodium-binding benzofuran isophthalate (SBFI). Hyperpolarization of spontaneously active dopamine neurons (recorded in current-clamp mode) caused the cessation of action potential firing accompanied by an elevation in [Na+]i. In dopamine neurons voltage-clamped at a holding potential of -60 mV elevations of [Na+]i were induced by long-lasting (45-60 s) voltage jumps to more negative membrane potentials (-90 to -120 mV) but not by corresponding voltage jumps to -30 mV. These hyperpolarization-induced elevations of [Na+]i were depressed during inhibition of I(h), a hyperpolarization-activated inward current, by Cs+. Hyperpolarization-induced elevations in [Na+]i might occur also in other cell types which express a powerful I(h) and might signal lack of postsynaptic activity. 相似文献
996.
AIM: The quality of segmentation and three-dimensional reconstruction of anatomical structures in tomographic slices is often impaired by disturbances due to partial volume effects (PVE). The potential for artefact reduction by use of the morphological image processing operators (MO) erosion and dilation is investigated. DESIGN: The CT examinations of 31 patients with pathological alterations in lung or brain were segmented using automatic region growing and the MO were applied in a different number of iterations. The processed regions were 3D-reconstructed (shaded surface display, MIP, volume rendering) and the occurrence of PVE-related artefacts using the signal-to-background ratio (SBR) prior to and after MO application was compared. RESULTS: For all patients under review, the artefacts caused by PVE were significantly reduced by erosion (lung: mean SBRpre = 1.67, SBRpost = 4.83; brain: SBRpre = 1.06, SBRpost = 1.29) even with only a small number of iterations. Region dilation was applied to integrate further structures (e.g. at tumor borders) into a configurable neighbourhood for segmentation and quantitative analysis. CONCLUSIONS: The MO represent an efficient approach for the reduction of PVE artefacts in 3D-CT reconstructions and allow optimized visualization of individual objects. 相似文献
997.
This paper is concerned with improvement in optical image quality by image restoration. Image restoration is an ill-posed
inverse problem which involves the removal or minimization of degradations caused by noise and blur in an image, resulting
from, in this case, imaging through a medium. Our work here concerns the use of the underlying Toeplitz structure of such
problems, and associated techniques for accelerating the convergence of iterative image restoration computations. Denoising
methods, including total variation minimization, followed by segmentation-based preconditioning methods for minimum residual
conjugate gradient iterations, are investigated. Regularization is accomplished by segmenting the image into (smooth) segments
and varying the preconditioners across the segments. By taking advantage of the Toeplitz structure, our algorithms can be
implemented with computational complexity of onlyO (ln
2 logn), wheren
2 is the number of pixels in the image andl is the number of segments used. Also, parallelization is straightforward. Numerical tests are reported for atmospheric imaging
problems, including the case of spatially varying blur.
Research supported in part by a National Science Foundation Postdoctoral Research Fellowship.
Research sponsored by the U.S. Air Force Office of Scientific Research under grant F49620-97-1-1039.
Research sponsored by the U.S. Air Force Office of Scientific Research under grant F49620-97-1-0139, and by the National Science
Foundation under grant CCR-96-23356.
Research sponsored by the National Science Foundation under grant CCR-96-23356. 相似文献
998.
C Jurinke B Z?llner HH Feucht D van den Boom A Jacob S Polywka R Laufs H K?ster 《Canadian Metallurgical Quarterly》1998,14(3):97-102
DNA preparations from three different groups of serum samples were examined for HBV-DNA via a nested polymerase chain reaction assay (lower detection limit: 10 viral genomes in 100 microliters serum): Group I consisted of 11 uninfected control sera, group II consisted of sera obtained from 11 HBV infected patients and group III consisted of 21 isolated anti-HBc positive samples. The 21 samples from group III were HBV-DNA negative according to a conventional non-nested PCR assay and hybridization with a 32P-labelled probe. Using nested PCR and mass spectrometry, HBV-DNA was detected in none of group I and in all of group II samples. In 11 out of 21 (52%) of the isolated anti-HBc positive sera from group III, HBV-DNA was detected. No correlation was observed between HBV-DNA positivity and anti-HBc titers. Matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry provided a fast, sensitive and non-radioactive assay for the detection of PCR products without the need for gel electrophoresis or hybridization with labelled probes. 相似文献
999.
1000.
Immunological identification of candidate proteins involved in regulating active shape changes of outer hair cells 总被引:1,自引:0,他引:1
M Knipper U Zimmermann I K?pschall K Rohbock S Jüngling HP Zenner 《Canadian Metallurgical Quarterly》1995,86(1-2):100-110
By employing immunological methods, it has been demonstrated that myosin, myosin light chain (MLC) and myosin light chain kinase (MLCK) proteins in outer hair cells (OHC) are immunologically different from isoforms in platelets, smooth muscle and heart muscle, and are probably more related to isoforms found in red blood cells (RBC). Moreover, proteins related to band 3 protein (b3p) and protein 4.1 (p 4.1), ankyrin as well as fodrin and spectrin, but not glycophorin, have been identified in isolated OHCs. Both OHCs and RBC differ from other motile non-muscle cells in their lack of smooth muscle isoforms of actin, their common high levels of spectrin-, ankyrin- and band 3-like proteins, as well as the expression of the 80 kDa protein 4.1 isoform. The data support the notion that motility of OHC may be based upon regulation of the b3p/p 4.1/ankyrin complex, and thus may be reminiscent to the active shape changes in RBC. 相似文献