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Telomerase activity and terminal restriction fragment (TRF) length were examined in hepatocellular carcinoma (HCC). Telomerase activity was assayed by telomeric repeat amplification protocol (TRAP) connected with an internal telomerase assay standard (ITAS). The incidence of strong telomerase activity (highly variable level compared with the activity of non-cancerous liver tissue) was 79% in well, 84% in moderately, and 100% in poorly differentiated HCC, while 0% in non-cancerous liver tissues. The incidence of TRF length alteration (reduction or elongation) was 53% in HCC. The incidence of TRF alteration was significantly higher in HCC exceeding 3 cm in diameter, moderately or poorly differentiated in histology. Telomerase activity was not associated with TRF length alteration in HCC. In conclusion, strong telomerase activity and TRF length alteration increased with HCC tumor progressions.  相似文献   
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The majority of BALB/c mice immunized with the BCL1 lymphoma-derived idiotype (Id+) IgM and subsequently challenged with BCL1 tumor cells develop a state of tumor dormancy. The vast majority of dormant lymphoma cells are in cell cycle arrest, but there are also residual replicating cells. In the present studies, we attempted to define features of both the dormant lymphoma cells and the host that lead to escape from dormancy. Escape from dormancy occurs at a steady rate over a 2-year period, suggesting that it is a stochastic process. We found that, in the majority of mice, escape was due to the emergence of genetic variants that were no longer susceptible to the anti-Id-mediated induction of dormancy. Ten percent of these variants were Id-; the remainder were Id+ but could grow in the presence of anti-Id antibodies, suggesting that there were mutations in molecules involved in one or more mIg-mediated negative-signaling pathways. In two of five such escapees, alterations in either Syk, HS1, and/or Lyn were observed. In a small percentage of mice, a low titer of circulating anti-Id antibody before tumor challenge correlated with a subsequent, more rapid loss of dormancy.  相似文献   
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Citrullinemia is a human genetic disease caused by a deficient argininosuccinate synthetase. In fibroblasts established from a citrullinemia patient with a mutation at the 3' splice site of the terminal intron of the gene, three cryptic 3' splice sites; i.e., SA1275, SA1636, and SA1663, residing on the terminal exon were activated. The usage of the cryptic sites showed a gradient, with the most downstream site having the highest usage; i.e., SA1663 > SA1636 > SA1275. However, when these cryptic sites were relocated to the internal exon, SA1636 was used the most. The splice-site strength of SA1636 was at least 10-fold higher than that of SA1663 in this situation. The results suggest that the preferential usage of SA1663 residing on the terminal exon may depend on its proximity to the poly(A) signal rather than on the strength of the splice site. Furthermore, when the strength of the downstream-most splice site increased, almost all the RNAs spliced to this site. However, in the presence of the wild-type splice site, all the RNAs were processed to the authentic site. Apparently, the selection of splice site can be revealed only when the sites being selected do not differ too much in their strength. By using a naturally occurring human mutant gene as a model, this study reveals that polyadenylation may play an important role in the selection of splice site during terminal exon definition.  相似文献   
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A highly inbred line of Drosophila melanogaster was subdivided into replicate sublines that were subsequently maintained independently with 10 pairs of parents per generation. The parents were randomly sampled for 19 'unselected' sublines and artificially selected for high or low abdominal or sternopleural bristle number for 12 'selected' sublines (with 3 replicate selection lines/trait/direction of selection). Divergence in mean bristle number among the unselected sublines, and response of the selected sublines to selection, are attributable to the accumulation of new mutations affecting bristle number. The input of mutational variance per generation, VM, can be estimated from the magnitude of response or divergence, assuming neutrality of mutations affecting the bristle traits. We reared unselected lines at generations 222 and 224, and selected lines at generations 182-184 of mutation accumulation at each of three temperatures (18 degrees C, 25 degrees C, 28 degrees C), and estimated the mutational variance common to all environments and the mutational variance from genotype x environment interaction. For sternopleural bristle number, the mutational interaction variance was 26% of the mutational variance common to all temperatures, and the interaction variance was due to temperature x line interaction. For abdominal bristle number, the mutational interaction variance was 142% of the mutational variance common to all temperatures, and the interaction variance was due to interactions of temperature x line, sex x line, and temperature x sex x line. It is possible that segregating variation for bristle number is maintained partly by genotype x environment interaction, but information on the fitness profiles of mutations affecting bristle number in each environment will be necessary to evaluate this hypothesis quantitatively.  相似文献   
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OBJECTIVE: Observations on nutritional disorders were made by a physician inmate in a concentration camp before and during the Great Starvation in China. METHODS/RESULTS: Based on therapeutic response, many unique abnormalities should be considered as a part of clinical picture of malnutrition, such as mucocutaneous pigmentation, nail layering phenomena and intranail hemorrhage, palmar/plantar fissures, vegetative system crisis, a avitaminostic fevers, multiple premature beats, and enlargement of cartilage, lymph nodes, and submandibular glands. DISCUSSION: Thiamin deficiency should be also considered as one, if not the only, etiologic factor of several common disorders, including submandibular gland cyst, Baker's cyst, stenosing tenosynovitis, direct inguinal hernia, among others.  相似文献   
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OBJECTIVES: To describe international variation in anesthesia care and monitoring during cataract surgery and to discuss its implications for cost and safety. METHODS: A standardized questionnaire was sent to random samples of ophthalmologists in the United States, Canada, and Barcelona, Spain, and to all ophthalmologists in Denmark. The survey was conducted in 1993 and 1994. Certified ophthalmologists who had performed 1 or more cataract extractions in the previous year were eligible for enrollment. RESULTS: The response rates were 62% in the United States (n=148), 67% in Canada (n=276), 70% in Barcelona (n=89), and 80% in Denmark (n=82). The anesthetic technique for cataract surgery varied significantly between sites (P<.001). Surgeons reported that retrobulbar blocks were used for 46% of the cataract extractions in the United States, 70% in Canada, 66% in Denmark, and 31% in Barcelona. In Barcelona, general anesthesia was used for 23% of the cataract extractions; it was used for less than 3% of the extractions at the other 3 sites. Peribulbar blocks or topical anesthesia was used for the remaining extractions. In the United States, Canada, and Barcelona, surgeons reported that vital functions were monitored during more than 97% of the extractions and anesthesia surveillance was used during more than 78% of the extractions. In Denmark, ophthalmologists reported that vital functions were monitored and anesthesia surveillance was used for 1% of the cataract extractions (P<.001). CONCLUSIONS: Substantial international variation in anesthesia care and monitoring during cataract surgery was observed. The findings suggest a need for further research to determine whether less intensive monitoring is cost-effective.  相似文献   
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