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81.
C Schmidt H Pommerenke F Dürr B Nebe J Rychly 《Canadian Metallurgical Quarterly》1998,273(9):5081-5085
Physical forces play a fundamental role in the regulation of cell function in many tissues, but little is known about how cells are able to sense mechanical loads and realize signal transduction. Adhesion receptors like integrins are candidates for mechanotransducers. We used a magnetic drag force device to apply forces on integrin receptors in an osteoblastic cell line and studied the effect on tyrosine phosphorylation as a biochemical event in signal transduction. Mechanical stressing of both the beta1 and the alpha2 integrin subunit induced an enhanced tyrosine phosphorylation of proteins compared with integrin clustering. Application of cyclic forces with a frequency of 1 Hz was more effective than a continuous stress. Using Triton X-100 for cell extraction, we found that tyrosine-phosphorylated proteins became physically anchored to the cytoskeleton due to mechanical integrin loading. This cytoskeletal linkage was dependent on intracellular calcium. To see if mechanical integrin stressing induced further downstream signaling, we analyzed the activation of mitogen-activated protein (MAP) kinases and found an increased phosphorylation of MAP kinases due to mechanical stress. We conclude that integrins sense physical forces that control gene expression by activation of the MAP kinase pathway. The cytoskeleton may play a key role in the physical anchorage of activated signaling molecules, which enables the switch of physical forces to biochemical signaling events. 相似文献
82.
In Escherichia coli, chi is a recombination hotspot that stimulates RecBCD-dependent exchange at and to one side of itself. chi activity is highest at chi and decreases with distance from chi. The decrease in chi activity may be a simple property of the physical distance over which chi can stimulate recombination. Alternatively, the decay in chi activity with distance may reflect the high likelihood that chi-stimulated recombination occurs in a single chi-proximal act, to the exclusion of additional chi-stimulated exchanges more distal to chi. To test the models, we determined if chi activity decreases as a function of physical distance (i.e., DNA base pairs) or genetic distance (homologous DNA base pairs). Our results indicate that chi activity decays as a function of genetic distance. In addition, we found that the sbcB gene product (exonuclease I, a 3'-->5' ssDNA exonuclease) modulates the distance over which chi can act. In contrast, the recJ gene product (a 5'-->3' ssDNA exonuclease) does not alter the decay of chi activity. 相似文献
83.
84.
Fish embryos represent a class of multicompartmental biological systems that have not been successfully cryopreserved, primarily because of the lack of understanding of how water and cryoprotectants permeate the compartments. We are using the zebrafish embryo as a model to understand these kinetics. Zebrafish embryos have two major compartments, the blastoderm and the yolk, which is surrounded by the multinucleated yolk syncytial layer (YSL). We determined the water and cryoprotectant permeability in these compartments using two methods. First, we measured shrink/swell dynamics in optical volumetric experiments. Zebrafish embryos shrank over time and did not re-expand while immersed in dimethyl sulfoxide (DMSO) or propylene glycol. Second, we measured DMSO uptake with diffusion-weighted nuclear magnetic resonance spectroscopy. DMSO uptake was rapid during the first few minutes, then gradual thereafter. We used one- and two-compartment models to analyze the data and to determine the permeability parameters. We found that the two-compartment model provided a better fit to the data. On the basis of this model and in the presence of DMSO, the yolk and blastoderm had very similar water permeabilities (i.e., 0.01 and 0. 005 micron x min-1atm-1, respectively), but they had different DMSO permeabilities separated by three orders of magnitude (i.e., = 5 x 10(-6) and 1.5 x 10(-3) cm/min, respectively). The low solute permeability of the yolk predicted that the yolk/YSL compartment should be more susceptible to cryodamage. To test this, the yolk, blastoderm, and YSL were examined at the ultrastructural level after vitrification. Only the YSL incurred significant damage after freezing and thawing (p = 0.05). 相似文献
85.
AS Stein MR O'Donnell A Chai GM Schmidt A Nademanee PM Parker EP Smith DS Snyder A Molina DE Stepan R Spielberger G Somlo KA Margolin N Vora J Lipsett J Lee J Niland SJ Forman 《Canadian Metallurgical Quarterly》1996,14(8):2206-2216
PURPOSE: To evaluate in a prospective study the efficacy of autologous bone marrow transplantation (BMT) in adult patients with acute myelogenous leukemia (AML) in first remission, using a single course of high-dose Cytarabine (HD Ara-C) consolidation therapy as in vivo purging. PATIENTS AND METHODS: Sixty consecutive adult patients with AML in first complete remission (CR) were treated with HD Ara-C consolidation therapy as a method of in vivo purging before marrow collection. High-dose therapy consisted of fractionated total-body irradiation (FTBI) 12 Gy, intravenous etoposide 60 mg/kg, and cyclophosphamide 75 mg/kg, followed by reinfusion of cryopreserved marrow. RESULTS: Sixty patients underwent consolidation treatment with HD Ara-C with the intent to treat with autologous BMT. Sixteen patients were unable to proceed to autologous BMT (10 patients relapsed, one died of sepsis, one developed cerebellar toxicity, two had inadequate blood counts, and two refused). Forty-four patients underwent autologous BMT and have a median follow-up time of 37 months (range, 14.7 to 68.7) for patients who are alive with no relapse. The cumulative probability of disease-free survival (DFS) at 24 months in the intent-to-treat group is 49% (95% confidence interval [CI], 37% to 62%) and in those who actually underwent autologous BMT is 61% (95% CI, 46% to 74%). The probability of relapse was 44% (95% CI, 31% to 58%) and 33% (95% CI, 20% to 49%) for the intent-to-treat and autologous BMT patients, respectively. CONCLUSION: This approach offers a relatively high DFS rate to adult patients with AML in first CR. The results of this study are similar to those achieved with allogeneic BMT. 相似文献
86.
We present a methodology for compiler synthesis based on Mosses-Watt's action semantics. Each action in action semantics notation is assigned specific “analysis functions”, such as a typing function and a binding-time function. When a language is given an action semantics, the typing and binding-time functions for the individual actions compose into typing and binding-time analyses for the language; these are implemented as the type checker and static semantics processor, respectively, in the synthesized compiler. Other analyses can be similarly formalized and implemented. We show a sample language semantics and its synthesized compiler, and we describe the compiler synthesizer that we have developed. 相似文献
87.
J. D. Verhoeven W. A. Spitzig F. A. Schmidt P. D. Krotz E. D. Gibson 《Journal of Materials Science》1989,24(3):1015-1020
Heavily drawn Cu-Nb alloys display quite high ultimate tensile strengths. A modification to the consumable arc-casting technique used to prepare these alloys is shown to decrease the as-cast niobium dendrite diameter,t
0, and also increase strength. Evaluation of strength, niobium filament spacing and thickness data show that strength varies with as-cast niobium dendrite size as somewhere betweent
o
–0.36
tot
o
–0.50
. Splat-cooling techniques demonstrate that minimum niobium dendrite sizes as small as 0.22m are possible. These sizes are over a factor of 10 smaller than has been achieved by consumable arc casting, and it is therefore suggested that processing rapidly solidified powders of Cu-Nb alloys should have significant advantages for preparing high-strength heavily drawn Cu-Nb alloys. 相似文献
88.
Otto Richter Thomas Schmidt Hand Büning-Pfaue und Dietrich Reinhardt 《Zeitschrift für Lebensmitteluntersuchung und -Forschung A》1988,187(2):130-136
Zusammenfassung Es werden pharmakokinetische Modelle angegeben, um den Konzentrationsverlauf von Arzneimittelrückständen im Menschen zu berechnen, die mit der Nahrung aufgenommen werden. Dabei lassen sich zwei Kompartimentmodelle für die Kinetik in der Nahrung und im Menschen koppeln: Das erste System liefert die Anfangswerte (bzw. eine Folge von Anfangswerten) für das zweite System. Das Modell wird auf die Übertragung von Chloramphenicol durch Speisefische auf den Menschen und auf die Übertragung von Theophyin durch die Muttermilch auf gestillte Säuglinge angewendet. Durch Einführung einer günstigsten und ungünstigsten Parameterkombination werden Grenzverläufe für die Blutspiegel berechnet, die als Grundlage einer Rückstandsbewertung dienen können.
Residues of active substances following the consumption of contaminated food —Status report on the evaluation of residues based on two drugs
Summary Pharmacokinetic models are presented for the computation of time courses of blood levels of drugs in man following the consumption of contaminated food. Mathematically, two linear systems of differential equations are set up for the donor organism (e.g., trout) and for the recipient, (e.g., man), where the first system generates the initial conditions for the second. Models of this kind are applied to the transfer of chloramphenicol to man via carp and trout (which had previously been administered this drug) and to the transfer of theophylline to infants via breast milk. Limiting concentration profiles are computed by constructing the most favourable and most adverse combinations of parameters with respect to drug elimination in both the donor and recipient organism.相似文献
89.
Lisa Goedtke Heike Sprenger Ute Hofmann Felix F. Schmidt Helen S. Hammer Ulrich M. Zanger Oliver Poetz Albrecht Seidel Albert Braeuning Stefanie Hessel-Pras 《International journal of molecular sciences》2021,22(1)
Polycyclic aromatic hydrocarbons (PAHs) are environmental pollutants produced by incomplete combustion of organic matter. They induce their own metabolism by upregulating xenobiotic-metabolizing enzymes such as cytochrome P450 monooxygenase 1A1 (CYP1A1) by activating the aryl hydrocarbon receptor (AHR). However, previous studies showed that individual PAHs may also interact with the constitutive androstane receptor (CAR). Here, we studied ten PAHs, different in carcinogenicity classification, for their potential to activate AHR- and CAR-dependent luciferase reporter genes in human liver cells. The majority of investigated PAHs activated AHR, while non-carcinogenic PAHs tended to activate CAR. We further characterized gene expression, protein abundancies and activities of the AHR targets CYP1A1 and 1A2, and the CAR target CYP2B6 in human HepaRG hepatoma cells. Enzyme induction patterns strongly resembled the profiles obtained at the receptor level, with AHR-activating PAHs inducing CYP1A1/1A2 and CAR-activating PAHs inducing CYP2B6. In summary, this study provides evidence that beside well-known activation of AHR, some PAHs also activate CAR, followed by subsequent expression of respective target genes. Furthermore, we found that an increased PAH ring number is associated with AHR activation as well as the induction of DNA double-strand breaks, whereas smaller PAHs activated CAR but showed no DNA-damaging potential. 相似文献
90.
The solubility of sulfur in chromia has been studied in H2-H2O-H2S tagged with35S at 973 and 1173 K at low oxygen and sulfur partial pressures typical for coal gasification-systems. For monocrystalline samples, it has been shown that sulfur-containing species are only present adsorbed on the surface of the specimens and can be removed by ultrasonic cleaning in acetone. The surface coverage after 4 weeks of exposure to H2-H2O-H2S was between 2.8 and 19.3% of a monolayer. In polycrystalline chromia, sulfur was located only in pores and cracks of the sample. In dense, compact areas of the specimens the solubility of sulfur was below the detection limit of autoradiography, which was estimated to be better than 0.17 ppm. 相似文献