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21.
Studies were conducted to assess the utility of free solution capillary electrophoresis (CE) for monitoring the effects of selected excipients on the thermal denaturation of a model protein (Ribonuclease A, RNase A) at low pH. Thermal denaturation/unfolding experiments were conducted via temperature-controlled CE using a run buffer of 20 mM citric acid in the pH range of 2.3-3.1, with a marker peptide incorporated to correct for temperature-induced changes in endoosmotic flow. The effects of selected excipients on the thermal unfolding of RNase A were then evaluated by adding either sorbitol, sucrose, polyethylene glycol 400 (PEG 400) or 2-methyl-2,4-pentanediol (MPD) to the electrophoretic run buffer (pH 2.3). Confirmatory denaturation experiments were conducted under the same solution conditions using circular dichroism (CD) spectropolarimetry. Using temperature-controlled CE, an increase in solution pH from 2.3 to 2.7 and 3.1 resulted in an increase in transition temperatures of RNase A by approximately 8 and 13 degrees C, respectively. Similar shifts in transition temperatures were observed when thermal denaturation transitions were monitored by far-UV CD. Sorbitol (0.55-1.1 M) and sucrose (0.55 M) each shifted the denaturation transition temperatures of RNase A to higher values, whereas PEG 400 and MPD had minimal effect on the unfolding transition midpoint at the concentrations evaluated (0.55 M for each). The observed changes in the transition temperatures for RNase A as a function of pH and selected excipients were similar when measured by either CE or far-UV CD. These results support the utility of CE for monitoring the effects of neutral excipients on the thermal denaturation of a model protein under selected conditions. The widespread utility of the technique may be limited by the narrow temperature range of most commercial CE instruments and the need to use extreme pH conditions to monitor the complete denaturation transition. 相似文献
22.
KR Hande 《Canadian Metallurgical Quarterly》1998,1400(1-3):173-184
Agents which 'poison' the enzyme topoisomerase II, have proven to be useful drugs for cancer treatment. Six antineoplastic drugs, which target topoisomerase II (doxorubicin, daunorubicin, idarubicin, mitoxantrone, etoposide and teniposide) are currently approved for clinical use in the United States. In this paper, the strategies and goals of cancer chemotherapy are summarized for the non-clinician. The use, pharmacology and toxicity of each of the six currently approved topoisomerase II inhibiting agents are reviewed. 相似文献
23.
We have determined the nucleotide and encoded amino acid sequences of the capsid, membrane precursor, membrane, envelope, and nonstructural NS1 protein genes of a dengue-2 virus (D2-04) isolated from a patient in Hainan, China. The sequenced region contains a gene organization similar to that of other flaviviruses. The overall amino acid sequence similarity between D2-04 and other dengue-2 viruses is greater than 92%, whereas that between D2-04 and members of the other dengue serotypes is about 65%. 相似文献
24.
HS Keirstead JK Dyer GN Sholomenko J McGraw KR Delaney JD Steeves 《Canadian Metallurgical Quarterly》1995,15(10):6963-6974
Transections of the chicken spinal cord after the developmental onset of myelination at embryonic day (E) 13 results in little or no functional regeneration. However, intraspinal injection of serum complement proteins with complement-binding GalC or 04 antibodies between E9-E12 results in a delay of the onset of myelination until E17. A subsequent transection of the spinal cord as late as E15 (i.e., during the normal restrictive period for repair) results in neuroanatomical regeneration and functional recovery. Utilizing a similar immunological protocol, we evoked a transient alteration of myelin structure in the posthatching (P) chicken spinal cord, characterized by widespread "unravelling" of myelin sheaths and a loss of MBP immunoreactivity (myelin disruption). Myelin repair began within 7 d of cessation of the myelin disruption protocol. Long term disruption of thoracic spinal cord myelin was initiated after a P2-P10 thoracic transection and maintained for > 14 d by intra-spinal infusion of serum complement proteins plus complement-binding GalC or 04 antibodies. Fourteen to 28 d later, retrograde tract tracing experiments, including double-labeling protocols, indicated that approximately 6-19% of the brainstem-spinal projections had regenerated across the transection site to lumbar levels. Even though voluntary locomotion was not observed after recovery, focal electrical stimulation of identified brainstem locomotor regions evoked peripheral nerve activity in paralyzed preparations, as well as leg muscle activity patterns typical of stepping in unparalyzed animals. This indicated that a transient alteration of myelin structure in the injured adult avian spinal cord facilitated brainstem-spinal axonal regrowth resulting in functional synaptogenesis with target neurons. 相似文献
25.
Localization of sound sources by human listeners has been widely studied and theories and various models of the localization and hearing mechanism have been constructed. In the classical "duplex" theory, sound localization in azimuth is explained by interaural time or equivalently, phase differences at low frequencies, and by interaural amplitude differences at higher frequencies. Head related transfer functions (HRTF's) present a linear system approach to modeling localization by representing the direction-dependent transformation the sound undergoes at each ear. Localization in elevation is explained by directional differences in the HRTF's, which also explains monaural localization. We conjecture that the HRTF's evolved during the course of nature (due to the evolution of the shape and structure of the ear etc.) are optimal with respect to several physically realizable criteria. In this paper, we investigate the problem of defining the design constraints which when optimized yield a set of HRTF's for hearing and monaural vertical localization in an attempt to better understand, and if possible, duplicate nature's design. We pursue an engineer's design perspective and formulate a constrained optimization problem, where the desired set of HRTF's is optimized according to a cost function based on several criteria for localization, hearing and smoothness, and also by imposing physically realizable constraints on the HRTF's such as nonnegativity, energy etc. The value of the cost function for a candidate set of HRTF's is an indication of the similarity of that set of HRTF's with respect to the ideal solution (measured HRTF data). The final optimization results we present are similar to the actual HRTF's measured in human subjects, and the associated cost function values are found to be almost equal. This points to the fact that the optimization criteria defined are quite relevant. The significant outcome of this research is the identification of a relevant set of mathematical criteria that could be optimized in the human auditory system to facilitate good hearing and localization. These criteria along with the associated constraints represent the desirable characteristics of the HRTF's in an HRTF-based localization system, and could lead to a better understanding and modeling of the auditory system. 相似文献
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28.
R. A. Minamisawa L. E. R. Santos M. A. Parada K. R. P. Daghastanli P. Ciancaglini A. De Almeida 《仪器科学与技术》2013,41(1):97-104
Abstract Techniques applying digital images increasingly have been used in biology, medicine, physics, and other research areas. The image coordinates can represent light intensities values to be detected by a CCD. Based on this concept, a photometric system composed of a LED source and a digital camera as a detector was used for optical density measurements. Standards for permanganate, glucose, and protein solutions were determined by colorimetric methods using our device. Samples of protein of Pasteurella mutocida bacteria membrane and, also, fractions of rabbit kidney membrane, rich in Na, K‐ATPase, with unknown concentrations were dosed through the Hartree method using our photometric system. 相似文献
29.
A progressive fibrous myopathy may result from chronic intramuscular drug abuse. This complication may mimic other rheumatic disorders and early recognition may prevent disability. The patient described here presented with fixed flexion and extension contracture of hips and knees, respectively, after abusing meperidine and other agents for 3 years. Soft tissues of thighs and buttocks were "wood hard," EMG showed absence of action potentials in affected muscles, and biopsy revealed extensive replacement of muscle with dense, acellular fibrous tissue. Possible mechanisms are discussed. 相似文献
30.
Preoperative radiotherapy for adenocarcinoma of the rectosigmoid 总被引:2,自引:0,他引:2
Ninety-seven patients with adenocarcinoma of the rectosigmoid have been treated with high dose (5000-6000 rad) preoperative irradiation from 1960 through 1972 at the University of Oregon Health Sciences Center. Fifty-seven were initially clinically resectable and 40 were initially inoperable. Forty of the 57 initially clinically resectable patients had "curative" resections and are at risk for more than 5 years. An increase in 5-year survival (from 38% to 53%) and an absence of pelvic recurrence have occurred in those patients receiving preoperative irradiation and "curative" resection. Four of the 40 initially inoperable patients are alive without tumor. Three of the four survivors had irradiation and surgery; one had irradiation only. An additional four patients had no evidence of tumor at death. Tumor was totally sterilized by irradiation and nine patients and reduced to microfocal extent in an additional three of the 97 patients. Incidence of complications was no greater than has been reported in a surgical series from the same institution. 相似文献