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41.
A de novo satellited short arm of the Y chromosome possibly resulting from an unstable translocation
A satellited long arm of the Y chromosome (Yqs) is considered a normal variation, whereas the presence of a satellite on the short arm of the Y (Yps) has never been described in the literature. A Yps chromosome could be clinically significant if the translocation resulting in Yps has relocated the testis-determining gene, SRY, to another chromosome. A carrier of such a translocation would therefore be at increased risk for having XX male and XY female offspring. Here we describe the first reported case of de novo Yps present in a phenotypically normal male. This Yps chromosome was positive for C-banding and nucleolus organizer region (NOR) staining and showed a hybridization signal for the beta-satellite sequence. Fluorescence in situ hybridization (FISH) analysis indicated that SRY was retained on the Yps and the translocation breakpoint on Yps was distal to the pseudoautosomal region. At prenatal diagnosis, a normal appearing Y chromosome was found in his son, and thus the satellite on Yps was lost during meiotic Xp-Yp pairing. This Yps chromosome was likely the product of an "unstable" translocation. 相似文献
42.
The efficacy of targeted therapeutics such as immunotoxins is directly related to both the extent of distribution achievable and the degree of drug internalization by individual cells in the tissue of interest. The factors that influence the tissue distribution of such drugs include drug transport; receptor/drug binding; and cellular pharmacology, the processing and routing of the drug within cells. To examine the importance of cellular pharmacology, previously treated only superficially, we have developed a mathematical model for drug transport in tissues that includes drug and receptor internalization, recycling, and degradation, as well as drug diffusion in the extracellular space and binding to cell surface receptors. We have applied this "cellular pharmacology model" to a model drug/cell system, specifically, transferrin and the well-defined transferrin cycle in CHO cells. We compare simulation results to models with extracellular diffusion only or diffusion with binding to cell surface receptors and present a parameter sensitivity analysis. The comparison of models illustrates that inclusion of intracellular trafficking significantly increases the total transferrin concentration throughout much of the tissue while decreasing the penetration depth. Increasing receptor affinity or tissue receptor density reduces permeation of extracellular drug while increasing the peak value of the intracellular drug concentration, resulting in "internal trapping" of transferrin near the source; this could account for heterogeneity of drug distributions observed in experimental systems. Other results indicate that the degree of drug internalization is not predicted by the total drug profile. Hence, when intracellular drug is required for a therapeutic effect, the optimal treatment may not result from conditions that produce the maximal total drug distribution. Examination of models that include cellular pharmacology may help guide rational drug design and provide useful information for whole body pharmacokinetic studies. 相似文献
43.
CL Quinn 《Canadian Metallurgical Quarterly》1998,26(9):665-667
Failure to achieve anesthesia can be a significant problem in the day-to-day practice of dentistry. The usual strategy following an anesthetic failure is to reinject. Therefore, a good understanding of conventional anesthetic techniques is important. But the practitioner also needs to have a broad armamentarium of injection strategies available for the "difficult-to-anesthetize cases". These strategies include the use of 5 percent lidocaine, intrapulpal injection, periodontal ligament injection and intraosseous injection. This paper will be a brief discussion of those techniques with an emphasis on the intraosseous injection. 相似文献
44.
PA Stumbles JA Thomas CL Pimm PT Lee TJ Venaille S Proksch PG Holt 《Canadian Metallurgical Quarterly》1998,188(11):2019-2031
Consistent with their role in host defense, mature dendritic cells (DCs) from central lymphoid organs preferentially prime for T helper cell type 1 (Th1)-polarized immunity. However, the "default" T helper response at mucosal surfaces demonstrates Th2 polarity, which is reflected in the cytokine profiles of activated T cells from mucosal lymph nodes. This study on rat respiratory tract DCs (RTDCs) provides an explanation for this paradox. We demonstrate that freshly isolated RTDCs are functionally immature as defined in vitro, being surface major histocompatibility complex (MHC) II lo, endocytosishi, and mixed lymphocyte reactionlo, and these cells produce mRNA encoding interleukin (IL)-10. After ovalbumin (OVA)-pulsing and adoptive transfer, freshly isolated RTDCs preferentially stimulated Th2-dependent OVA-specific immunoglobulin (Ig)G1 responses, and antigen-stimulated splenocytes from recipient animals produced IL-4 in vitro. However, preculture with granulocyte/macrophage colony stimulating factor increased their in vivo IgG priming capacity by 2-3 logs, inducing production of both Th1- and Th2-dependent IgG subclasses and high levels of IFN-gamma by antigen-stimulated splenocytes. Associated phenotypic changes included upregulation of surface MHC II and B7 expression and IL-12 p35 mRNA, and downregulation of endocytosis, MHC II processing- associated genes, and IL-10 mRNA expression. Full expression of IL-12 p40 required additional signals, such as tumor necrosis factor alpha or CD40 ligand. These results suggest that the observed Th2 polarity of the resting mucosal immune system may be an inherent property of the resident DC population, and furthermore that mobilization of Th1 immunity relies absolutely on the provision of appropriate microenvironmental costimuli. 相似文献
45.
Mouse pancreatic islet grafts under the kidney capsule of syngeneic hosts were removed and perifused in vitro 1-40 weeks after the transplantation. In comparison with fresh islets, 12- to 40-week-old grafts exhibited an attenuated first phase of glucose-stimulated insulin release. In grafts 1, 12, 28, or 40 weeks old, but not in fresh islets, the mean secretory rate during the initial 10 min of stimulation was significantly lower than that during the subsequent 15 min. When expressed in relation to insulin content, the insulin output in response to 11 mmol/L glucose was no less from grafts than from fresh islets; in grafts 12 or 40 weeks old at 16.7 mmol/L glucose, the fractional output above baseline was significantly diminished during the initial 10 min, but not subsequently. Immediately on switching from basal to stimulatory glucose concentration, there was a transient drop in insulin secretion from the grafts, especially after more than 12 weeks of transplantation and in response to 16.7, as compared with 11, mmol/L glucose. When glucose was switched back from stimulatory to basal concentration, grafts also frequently exhibited a transient increase in the insulin secretory rate. Neither initial drops nor "off responses" were seen in untransplanted islets. The modifications of the secretory dynamics in islet grafts suggest that transplantation influences the balance between the stimulatory and inhibitory influences of glucose on the beta-cell's secretory machinery. 相似文献
46.
47.
M Pazianas M Zaidi CL Huang BS Moonga VS Shankar 《Canadian Metallurgical Quarterly》1993,192(3):1100-1105
We demonstrated previously that osteoclasts possess a divalent cation-sensitive "receptor", the Ca2+ receptor. Activation of the Ca2+ receptor by the surrogate cation Ni2+ was shown to elicit an increase in cytosolic [Ca2+] to a peak value followed by an exponential decline. In the present study we examined the influence of surface membrane voltage on the kinetics of Ca2+ receptor inactivation. The K+ ionophore, valinomycin was applied to intercept the declining phase of the cytosolic [Ca2+] transient elicited by application of between 50 microM- and 5 mM-[Ni2+]. This resulted in a sustained elevation of cytosolic [Ca2+] or even a 'hump' followed by a gradual decline. Such a kinetic alteration persisted in a Ca(2+)-free solution, but was abolished in high extracellular [K+] (105 mM). Thus, we demonstrate for the first time to our knowledge, a modulatory effect of membrane potential on the function of the osteoclast Ca2+ receptor. 相似文献
48.
49.
Haider F. Abdul Amir Abdulah Chik 《Nuclear instruments & methods in physics research. Section B, Beam interactions with materials and atoms》2009,267(18):3032-3036
The main purpose of this study is to provide the knowledge and data on Deuterium-Tritium (D-T) fusion neutron induced damage in MOS devices. Silicon metal oxide semiconductor (MOS) devices are currently the cornerstone of the modern microelectronics industry. However, when a MOS device is exposed to a flux of energetic radiation or particles, the resulting effects from this radiation can cause several degradation of the device performance and of its operating life. The part of MOS structure (metal oxide semiconductor) most sensitive to neutron radiation is the oxide insulating layer (SiO2). When ionizing radiation passes through the oxide, the energy deposited creates electron-hole pairs. These electron-hole pairs have been seriously hazardous to the performance of these electronic components. The degradation of the current gain of the dual n-channel depletion mode MOS caused by neutron displacement defects, was measured using in situ method during neutron irradiation. The average degradation of the gain of the current is about 35 mA, and the change in channel current gain increased proportionally with neutron fluence. The total fusion neutron displacement damage was found to be 4.8 × 10−21 dpa per n/cm2, while the average fraction of damage in the crystal of silicon was found to be 1.24 × 10−12. All the MOS devices tested were found to be controllable after neutron irradiation and no permanent damage was caused by neutron fluence irradiation below 1010n/cm2. The calculation results shows that (n,α) reaction induced soft-error cross-section about 8.7 × 10−14 cm2, and for recoil atoms about 2.9 × 10−15 cm2, respectively. 相似文献
50.