全文获取类型
收费全文 | 174篇 |
免费 | 18篇 |
专业分类
192篇 |
出版年
2022年 | 2篇 |
2021年 | 3篇 |
2018年 | 2篇 |
2016年 | 3篇 |
2015年 | 3篇 |
2014年 | 7篇 |
2013年 | 7篇 |
2012年 | 6篇 |
2011年 | 4篇 |
2010年 | 5篇 |
2009年 | 5篇 |
2008年 | 11篇 |
2007年 | 8篇 |
2006年 | 6篇 |
2005年 | 9篇 |
2004年 | 10篇 |
2003年 | 4篇 |
2002年 | 5篇 |
2001年 | 9篇 |
2000年 | 6篇 |
1999年 | 3篇 |
1998年 | 8篇 |
1995年 | 2篇 |
1994年 | 3篇 |
1993年 | 1篇 |
1992年 | 5篇 |
1991年 | 4篇 |
1990年 | 2篇 |
1989年 | 6篇 |
1988年 | 3篇 |
1987年 | 3篇 |
1986年 | 2篇 |
1985年 | 5篇 |
1984年 | 2篇 |
1983年 | 2篇 |
1982年 | 1篇 |
1981年 | 2篇 |
1979年 | 5篇 |
1978年 | 2篇 |
1977年 | 1篇 |
1974年 | 1篇 |
1973年 | 1篇 |
1972年 | 2篇 |
1971年 | 2篇 |
1970年 | 1篇 |
1969年 | 1篇 |
1965年 | 1篇 |
1960年 | 2篇 |
1936年 | 1篇 |
1914年 | 1篇 |
排序方式: 共有192条查询结果,搜索用时 15 毫秒
1.
Regulation of natural killer cell activity by macrophages in the rheumatoid joint and peripheral blood 总被引:3,自引:0,他引:3
B Combe R Pope B Darnell W Kincaid N Talal 《Journal of immunology (Baltimore, Md. : 1950)》1984,133(2):709-713
Recently, in another study, we observed that indomethacin, a prostaglandin synthetase inhibitor, significantly increased NK activity in both normal and rheumatoid arthritis (RA) peripheral blood (PB) but not in RA synovial fluid (SF). Because macrophages are a major source of prostaglandins, we examined the effect of macrophage-enriched adherent cells (AC) on NK activity as measured by a 3-hr Cr-release assay with K 562 cells. The removal of AC resulted in increased (p less than 0.01) NK activity in both normal and RA PB. In contrast, the removal of AC from RA SF resulted in a significant decrease (p less than 0.001) of NK activity. By using only nonadherent cells (NAC), NK activity in RA SF and synovial tissue (ST) was significantly reduced when compared to autologous RA PB (p less than 0.001). Enhancement of NK activity of SF NAC by both poly I:C and IL 2 was not dependent on AC. Mixing experiments demonstrated that the addition of synovial AC for 16 hr increased NK activity of synovial NAC to a level similar to that of unseparated mononuclear cells, whereas autologous PB AC suppressed NK activity of PB NAC. PB AC, when added to SF NAC, also increased NK activity. Supernatants from synovial mononuclear cells were stimulatory of synovial NAC NK activity, whereas normal PB mononuclear supernatants were suppressive. These observations document 1) a significant reduction of NAC-mediated NK activity in the rheumatoid joint as compared to PB from the same patient, and 2) that AC modulate NK activity differently in the rheumatoid joint as compared to RA or normal PB. 相似文献
2.
A rapid non-radioactive procedure for plaque hybridization using biotinylated probes prepared by random primed labeling 总被引:3,自引:0,他引:3
A simple, non-radioactive method has been developed for the rapid screening of phage libraries. In the present study, nanogram amounts of a small restriction fragment (135 bp) were biotinylated via random primed labeling and used to probe cDNA libraries using a modified plaque hybridization protocol. The high backgrounds that are seen typically with avidin/biotin-based methods for plaque hybridization were eliminated by incubation of filters with one of several different proteases prior to hybridization. A comparison of several detection systems indicated that streptavidin conjugated to calf intestinal alkaline phosphatase (AP) was the most sensitive, yielding signals comparable to those obtained with 32P-labeled probes. The times required for phage growth and pre-hybridization were reduced substantially, permitting a convenient one-day screening protocol. Nitrocellulose filters gave the best signal to noise ratio, although "streaking" of plaque DNA was observed occasionally; this problem can be overcome by using nylon-based membranes, which allows exact visualization of the positive plaques. The method was highly reliable; 29 out of 33 putative clones retested positive and the authenticity of these was confirmed by DNA sequence analysis. The random primed biotinylation procedure has been utilized successfully with several different cDNA fragments and has proven useful for other hybridization-based methods (Northern and Southern blots), without the problems associated with the use of radiolabeled probes. 相似文献
3.
Hardies SC; Martin SL; Voliva CF; Hutchison CA d; Edgell MH 《Molecular biology and evolution》1986,3(2):109-125
4.
Polyacrylamide vertical gel electrophoresis was used to separate the caseins of sows' milk. Polymorphism was found in a region of the gels designated Cn3. The Cn3 polymorphism consists of two bands which appear to be controlled by two codominant alleles designated Cn
3
A
and Cn
3
B
. Homozygotes possess one band and heterozygotes posses both bands of equal intensity giving the following phenotypes: Cn3A, Cn3AB, and Cn3B. A chi-square test for goodness of fit of the observed phenotypes to that expected by the Hardy-Weinberg equilibrium formula and a segregation analysis of eight matings involving 19 female progeny conform to the hypothesis that the Cn3 polymorphism is controlled by two codominant autosomal alleles. Further family studies will be necessary to confirm the genetic control of the Cn3 polymorphism.Deceased. 相似文献
5.
The calmodulin-dependent protein phosphatase catalytic subunit (calcineurin A) is an essential gene in Aspergillus nidulans. 总被引:5,自引:1,他引:4 下载免费PDF全文
C Rasmussen C Garen S Brining R L Kincaid R L Means A R Means 《The EMBO journal》1994,13(11):2545-2552
The gene encoding the homologue of the catalytic subunit of the Ca2+/calmodulin-regulated protein phosphatase 2B (calcineurin A) has been isolated from Aspergillus nidulans. This gene, cnaA+, is essential in this fungal system. Analysis of growth-arrested cells following gene disruption by homologous recombination reveals that they are blocked early in the cell cycle. The cnaA+ gene encodes a 2.5 kb mRNA and the deduced protein sequence is highly homologous to the calcineurin A subunit of other species. The mRNA varies in a cell cycle-dependent manner with maximal levels found early in G1 and considerably before the G1/S boundary. As calmodulin is also essential for A.nidulans cell cycle progression and levels rise before the G1/S boundary, our data suggest that calcineurin may represent a primary target for calmodulin at this cell cycle transition point. 相似文献
6.
Calcineurin is associated with the cytoskeleton of cultured neurons and has a role in the acquisition of polarity. 总被引:5,自引:0,他引:5 下载免费PDF全文
Calcineurin is a calmodulin-dependent serine-threonine phosphatase found in many cell types but most abundant in neurons. To determine its localization in developing neurons, dissociated cultures from embryonic day 15 rat cerebellum were analyzed immunocytochemically after treatment with cytoskeletal-disrupting drugs. During the initial outgrowth of neurites, calcineurin is enriched in growth cones where its localization depends upon the integrity of both microtubules and actin filaments. Treatment with cytochalasin shifts calcineurin from the growth cone to the neurite shaft, and with nocadozole calcineurin translocates to the cell body. Therefore calcineurin is well positioned to mediate interactions between cytoskeletal systems during neurite elongation. By 14 d in culture, when the neurons have developed extensive neuronal contacts and synapses are present, calcineurin is predominantly in the neurite shaft. Incubation of cultured cells with Cyclosporin A or a specific peptide, both of which selectively inhibit calcineurin's phosphatase activity, prevented axonal elongation. Because the microtubule-associated protein tau appears to play a key role in asymmetric neurite elongation, we examined modifications in its phosphorylation state resulting from calcineurin inhibition. In contrast to the normal development of cerebellar macroneurons in which reactivity with the phosphorylation-dependent antibody, tau-1, progressively increases, there was a persistent inhibition of tau-1 reactivity in cells exposed to Cyclosporin A. These findings suggest a role for calcineurin in regulating tau phosphorylation and possibly modulating other steps required for the determination of polarity. 相似文献
7.
Trees of Sassafras albidum (Nuttall) Nees. display leaves that fall into discrete categories of form. Unlobed leaves, with undissected margins, predominate at proximal and distal nodes of shoots, while lobed leaves are most common at intermediate nodes. In this study we investigated the hypothesis that shoots of sassafras respond to environmental changes over the growing season by generating predictable nodal patterns for leaf morphology and physiology. We recorded leaf shape category and measured leaf surface area, node number, chlorophyll content, nitrogen content, and photosynthesis in four trees. Over 1,000 measurements of photosynthesis were made in situ, using the LI-Cor LI 6200 portable photosynthesis system. The two trees growing under heavy shade had few lobed leaves (2.0% and 18.8%) and often had negative carbon balance, with positive net photosynthesis occurring during sun flecks. The two trees growing in more open conditions had many more lobed leaves (56.3% and 61.0%) and higher, less variable net photosynthetic rates. As indicated by chlorophyll and nitrogen contents, the highest leaf photosynthetic rates occurred at intermediate nodes (nodes six to nine), and this was shifted distally along the shoot during the growing season. Leaves at intermediate nodes also had the largest surface areas and the greatest frequency of lobing. In comparative experiments with models, lobing was shown to enhance free-convectional heat loss relative to unlobed leaves of the same surface area. Due to their large surface area, these leaves also have the highest rates of whole leaf photosynthesis. Under conditions of equivalent photosynthetically active radiation, lobed leaves had higher rates of net photosynthesis than did unlobed leaves. We conclude that shoots of sassafras produce groups of leaves with predictably different morphological and physiological specializations. 相似文献
8.
The effect of several inhibitors of the enzyme cyclic 3',5'-AMP phosphodiesterase as chemoattractants in Physarum polycephalum was examined. Of the compounds tested, 4-(3-butoxy-4-methoxybenzyl)-2-imidazolidinone (Roche 20-1724/001) and 1-ethyl-4-(isopropylidinehydrazino)-1H-pyrazolo-(3,4-b)-pyridine-5-carboxylic acid ethyl ester, hydrochloride (Squibb 20009) were the most potent attractants. 3-Isobutyl-1-methyl xanthine, theophylline, and morin (a flavanoid) were moderate attractants and sometimes gave negative chemotaxis at high concentrations. Cyclic 3',5'-AMP was an effective, but not potent attractant. A repellent effect following the positive chemotactic action was sometimes observed with cyclic 3',5'-AMP at concentrations as high as 1 . 10(-2) M. Dibutyryl cyclic AMP appeared to be a somewhat more potent attractant than cyclic 3',5'-AMP. The 8-thiomethyl and 8-bromoderivatives of cyclic AMP, which are poorly hydrolyzed by the phosphodiesterase, were not attractants in Physarum. Possible participation of cyclic 3',5'-AMP in the directional movement in P. polycephalum is discussed. 相似文献
9.
Chun Jung Chen Jennifer E. Cox Rodney P. Kincaid Angel Martinez Christopher S. Sullivan 《Journal of virology》2013,87(20):11135-11147
Hundreds of virus-encoded microRNAs (miRNAs) have been uncovered, but an in-depth functional understanding is lacking for most. A major challenge for the field is separating those miRNA targets that are biologically relevant from those that are not advantageous to the virus. Here, we show that miRNAs from related variants of the polyomavirus simian vacuolating virus 40 (SV40) have differing host target repertoires (targetomes) while their direct autoregulatory activity on virus-encoded early gene products is completely preserved. These results underscore the importance of miRNA-mediated viral gene autoregulation in some polyomavirus life cycles. More broadly, these findings imply that some host targets of virus-encoded miRNAs are likely to be of little selective advantage to the virus, and our approach provides a strategy for prioritizing relevant targets. 相似文献
10.
Inheritance of microsatellite loci in the polyploid lake sturgeon (Acipenser fulvescens). 总被引:1,自引:0,他引:1
Inheritance in the expression of amplicons for four microsatellite primer pairs was determined using 10 families created from gametes of wild lake sturgeon (Acipenser fulvescens). Loci Afu34 and Afu68 expressed a maximum of two even-intensity bands per individual and had progeny genotype ratios that fit disomic inheritance (P > 0.05). Some variation exhibited at Afu34 and Afu68 was attributable to a null allele. Genotype expression at both loci also indicated that one female parent had transmitted unreduced gametes. Primer Afu39 amplified products that exhibited four gene doses, where genotype counts fit expected ratios for disomic inheritance (P > 0.05) indicating amplification of products from two disomic loci that share alleles. Meiotic drive was evident at the Afu39 loci based on a test for random segregation (P < 0.05). Only the expression of Afu19 gave evidence of tetrasomic inheritance based on a single progeny potentially produced by a double reduction gamete. No evidence for proposed octoploid inheritance was observed. 相似文献