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161.
Neurons undergo complex morphological changes during differentiation and in cases of plasticity. A major determinant of cell morphology is the actin cytoskeleton, which in neurons is comprised of two actin isoforms, non-muscle gamma- and beta-actin. To better understand their respective roles during differentiation and plasticity, their cellular and subcellular localization was examined in developing and adult cerebellar cortex. It was observed that gamma-actin is expressed at a constant level throughout development, while the level of beta-actin expression rapidly decreases with age. At the light microscopic level, gamma-actin staining is ubiquitous and the only developmental change observed is a relative reduction of its concentration in cell bodies and white matter. In contrast, beta-actin staining almost completely disappears from the cytoplasm of cell bodies, primary dendrites and axons. In young cerebellar cultures, gamma-actin is found in the cell body, neurites and growth cones, while beta-actin is mainly found in growth cones, as previously reported in other primary neuronal culture systems [Kaech et al. (1997), J. Neuroscience, 17, 9565-9572; Bassell et al., (1998), J. Neuroscience, 18, 251-265]. Electron microscopy of post-embedding immunogold-labelled tissue confirms the widespread distribution of gamma-actin, and also reveals an increased concentration of gamma-actin in dendritic spines in the adult. During development, beta-actin accumulation is observed in actively growing structures, e.g., growth cones, filopodia, cell bodies and axonal tracts. In the adult cerebellar cortex, beta-actin is preferentially found in dendritic spines, structures which are known to retain their capacity for morphological modifications in the adult brain. This differential subcellular localization and developmental regulation of the two actin isoforms point to their different roles in neurons.  相似文献   
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Potent, non-peptidic, dihydropyrone sulfonamide HIV protease inhibitors have been previously described. Crystallographic analysis of dihydropyrone sulfonamide inhibitor/HIV protease complexes suggested incorporation of a second, C2 symmetry-related sulfonamide group. Selected bis-sulfonamide dihydropyrone analogues display high HIV protease inhibitory activity.  相似文献   
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The authors present an algorithm utilizing Markov random field modeling for identifying lung regions in a digitized chest radiograph (DCR). Let x represent the classifications of each pixel in a DCR as either lung or nonlung. We model x as a realization of a spatially varying Markov random field. This model is developed utilizing spatial and textural information extracted from samples of lung and nonlung region-types in a training set of DCRs. With this model, the technique of Iterated Conditional Modes is used to determine the optimal classification of each pixel in a DCR. The algorithm's ability to identify lung regions is evaluated on a testing set of DCRs. The algorithm performs well yielding a sensitivity of 90.7% +/- 4.4%, a specificity of 97.2% +/- 2.0%, and an accuracy of 94.8% +/- 1.6%. In an attempt to gain insight into the meaning and level of the algorithm's performance numbers, the results are compared to those of some easily implemented classification algorithms.  相似文献   
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The glucocorticoid receptor (GR) is recovered from hormone-free cells in a heterocomplex with the molecular chaperone hsp90, which is required to produce the proper folding state for steroid binding. GR.hsp90 heterocomplexes are formed by a multiprotein system that appears to exist in all eukaryotic cells. Recently, we have reconstituted a receptor.hsp90 heterocomplex assembly system with purified rabbit hsp90 and hsp70 and bacterially expressed human p23 and p60. We have shown that hsp90, p60, and hsp70 form an hsp90.p60. hsp70 complex that converts the GR from a non-steroid binding to a steroid binding form (Dittmar, K. D., and Pratt, W. B. (1997) J. Biol. Chem. 272, 13047-13054). The resulting GR.hsp90 heterocomplex rapidly disassembles unless p23 is present to bind to the ATP-dependent conformation of hsp90 and stabilize its association with the receptor (Dittmar, K. D., Demady, D. R., Stancato, L. F., Krishna, P., and Pratt, W. B. (1997) J. Biol. Chem. 272, 21213-21220). In the current work, we show that the purified rabbit hsp70 utilized in prior studies is contaminated with a small amount of the rabbit DnaJ homolog hsp40. Elimination of the hsp40 from the purified GR.hsp90 assembly system reduces assembly activity, and the activity is restored by addition of the purified yeast DnaJ homolog YDJ-1. hsp40 is a component of the hsp90.p60.hsp70 foldosome complex isolated from reticulocyte lysate with antibody against p60. Under conditions that promote binding of p23 to hsp90 (elevated temperature, ATP, Nonidet P-40, molybdate), a five-membered (p23. hsp90.p60.hsp70.hsp40) complex of chaperone proteins is formed in reticulocyte lysate or from purified proteins. The hsp40-free, purified assembly system has a modest level of assembly activity that is maximally potentiated by YDJ-1 when it is present at about one-twentieth the concentration of hsp70. Although hsp40 is not in the final GR.hsp90 heterocomplex isolated from L cell cytosol, it is in the GR.hsp90 heterocomplex assembled in reticulocyte lysate. We conclude that hsp40 is a component of the multiprotein hsp90-based chaperone system where it potentiates GR.hsp90 heterocomplex assembly.  相似文献   
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OBJECTIVE: To evaluate the results of cervical cytology screening in the National Breast and Cervical Cancer Early Detection Program and to compare the findings with results from other screening programs. METHODS: We analyzed data on 312,858 women aged 18 years and older who received one or more Papanicolaou smears, and follow-up if indicated, from October 1991 through June 1995 at screening sites across the United States providing comprehensive National Breast and Cervical Cancer Early Detection Program services. RESULTS: Of the women screened, more than half were 40 years or older; slightly less than half (44%) were of racial and ethnic minorities. During the first screening cycle, 3.8% of Papanicolaou tests were reported as abnormal (squamous intraepithelial lesion [SIL] or squamous cell cancer); proportions of abnormals decreased with increasing age. The age-adjusted rate of biopsy-confirmed cervical intraepithelial neoplasia (CIN) II or worse among women screened was 7.4 per 1000 Papanicolaou tests; rates of CIN were highest among young women, but cancer rates peaked among women in their 50s and 60s. The percentages of first screening cycle-Papanicolaou tests interpreted as high-grade SIL and squamous cell carcinoma associated with biopsy-confirmed CIN II or worse (the positive predictive value) were 56.0% for CIN II/III and 3.7% for invasive cancer. Of the 150 invasive cancers diagnosed, 54.0% were classified as local disease. CONCLUSION: Observed results emphasize the duality of cervical neoplasia-CIN in younger women and invasive cancer in older women. This finding points to the importance of reaching both younger and older women for cervical cancer screening.  相似文献   
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