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排序方式: 共有178条查询结果,搜索用时 171 毫秒
41.
Bebb DG Warrington PJ de Jong G Yu Z Moffat JA Skov K Spacey S Gelmon K Glickman BW 《Mutation research》2001,476(1-2):13-20
Recent reports suggest that the radiation-induced, p53-dependent, apoptotic response is aberrant in ataxia telangiectasia (AT) cells. We investigated the possibility that an aberrant apoptotic response to ionizing radiation may also be the characteristic of AT heterozygotes and may facilitate in discriminating AT heterozygotes from the general population. Log phase, Epstein Barr virus (EBV) transformed lymphoblastoid cell lines and primary lymphocytes from three AT families were irradiated and the apoptotic response at 30h post radiation was measured by flow cytometry using TUNEL and hypodiploid methods. Our results show that the apoptotic response of AT homozygote (ATM-/-), AT heterozygote (ATM+/-) and normal cells (ATM+/+) to ionizing radiation, measured by the hypodiploid and TUNEL methods using flow cytometry, is dose and time dependent. Furthermore, this response is paradoxical in that ATM (-/-) lymphoblastoid cells were characterized by a reduced post radiation apoptotic response compared to their normal counterparts. Heterozygote (ATM+/-) lymphoblastoid cells displayed an intermediate response to ionizing radiation. In contrast, primary, non-transformed AT cells exhibited the same apoptotic response as their normal counterparts. Our results thus indicate that pre-radiation, EBV-transformed, lymphoblastoid cell lines from individual families may be useful in discriminating ATM status, but patient-derived, primary AT homozygous, heterozygous and normal primary cultured lymphocytes cannot be discriminated by this assay. 相似文献
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We examined cytoplasmic trafficking and nuclear translocation of adeno-associated virus type 2 (AAV) by using Alexa Fluor 488-conjugated wild-type AAV, A20 monoclonal antibody immunocytochemistry, and subcellular fractionation techniques followed by DNA hybridization. Our results indicated that in the absence of adenovirus (Ad), AAV enters the cell rapidly and escapes from early endosomes with a t(1/2) of about 10 min postinfection. Cytoplasmically distributed AAV accumulated around the nucleus and persisted perinuclearly for 16 to 24 h. Viral uncoating occurred before or during nuclear entry beginning about 12 h postinfection, when viral protein and DNA were readily detected in the nucleus. Few, if any, intact AAV capsids were found in the nucleus. In the presence of Ad, however, cytoplasmic AAV quickly translocated into the nucleus as intact particles as early as 40 min after coinfection, and this facilitated nuclear translocation of AAV was not blocked by the nuclear pore complex inhibitor thapsigargan. The rapid nuclear translocation of intact AAV capsids in the presence of Ad suggested that one or more Ad capsid proteins might be altering trafficking. Indeed, coinfection with empty Ad capsids also resulted in the appearance of AAV DNA in nuclei within 40 min. Escape from early endosomes did not seem to be affected by Ad coinfection. 相似文献
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C. A. Mundy L. J. Allen-Williams N. Underwood S. Warrington 《Journal of Applied Entomology》2000,124(9-10):349-358
Abstract: Several authors have indicated that carabid beetles offer potential as predators of insect pests on arable crops, but this potential is reduced by their limited ability to climb the crop plants. In the current investigation an initial laboratory experiment indicated that seven species of carabid beetles commonly found in arable fields in the UK would feed on both aphid and collembolan prey. Pterostichus cupreus L. and Bembidion guttula Fabr. were found to accept both live and dead aphids and collembolans. In further laboratory investigations P. cupreus exhibited greater consumption of the cereal aphid Metopolophium dirhodum Walker than the alternative prey species Heteromurus nitidus , Templeton (Collembola, Entomobryidae) and there was some indication of preference for the aphid prey as these were often consumed first. Significantly more handling time was required for the consumption of M. dirhodum compared to H. nitidus. The treatments where P. cupreus was given a diet of aphids or collembolans prior to the prey choice experiment, did not appear to influence the number or type of prey items consumed.
Using a four-arm olfactometer P. cupreus reacted positively to the volatiles from collembolans, but gave a less clear response to those from the cereal aphid M. dirhodum . In an artificial field arena P. cupreus readily climbed barley plants in search of M. dirhodum , perhaps as a response to volatile emissions, but this behaviour changed when H. nitidus were introduced onto the substrate of the arena. Although the current results indicated that P. cupreus has potential for the control of cereal aphids, the presence of alternative prey appeared to reduce this potential and suggest that the carabid is an opportunistic feeder. 相似文献
Using a four-arm olfactometer P. cupreus reacted positively to the volatiles from collembolans, but gave a less clear response to those from the cereal aphid M. dirhodum . In an artificial field arena P. cupreus readily climbed barley plants in search of M. dirhodum , perhaps as a response to volatile emissions, but this behaviour changed when H. nitidus were introduced onto the substrate of the arena. Although the current results indicated that P. cupreus has potential for the control of cereal aphids, the presence of alternative prey appeared to reduce this potential and suggest that the carabid is an opportunistic feeder. 相似文献
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Regulation of macromolecular synthesis in reovirus-infected L-929 cells I. Effect of L-histidinol.
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The histidine analogue L-histidinol, reported by Vaughan and Hansen (1973) to establish a potent, readily reversible inhibition of eukaryotic protein synthesis in vivo, was used to investigate the regulation of macromolecular synthesis in reovirus-infected L-929 cells. The addition of L-histidinol to normal L cells led to a total inhibition of protein synthesis. The inhibition appeared to be a consequence neither of isotope dilution resulting from elevated endogenous amino acids nor of an inability of treated cells to accumulate exogenous amino acids. Addition of L-histidine to histidinol-arrested cells resulted in a complete recovery of protein synthesis. Similarly, protein synthesis in reovirus-infected L cells examined 17 h postinfection (31 C) was totally inhibited by histidinol treatment and was readily reversed by the addition of histidine. Reovirus-infected cells treated with histidinol had an essentially unaltered capacity to synthesize reovirus single-stranded RNA relative to unperturbed cultures but a diminishing ability to maintain genome RNA synthesis. Addition of L-histidine to arrested cultures led to a complete recovery of genome RNA synthesis. The L-histidinol-mediated arrest of protein synthesis was both very effective and easily reversed, suggesting the general applicability of this novel inhibitor to investigations of regulation of macromolecular synthesis in both normal and virus-infected eukaryotic cells. 相似文献
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Sovio U Mook-Kanamori DO Warrington NM Lawrence R Briollais L Palmer CN Cecil J Sandling JK Syvänen AC Kaakinen M Beilin LJ Millwood IY Bennett AJ Laitinen J Pouta A Molitor J Davey Smith G Ben-Shlomo Y Jaddoe VW Palmer LJ Pennell CE Cole TJ McCarthy MI Järvelin MR Timpson NJ;Early Growth Genetics Consortium 《PLoS genetics》2011,7(2):e1001307
An age-dependent association between variation at the FTO locus and BMI in children has been suggested. We meta-analyzed associations between the FTO locus (rs9939609) and BMI in samples, aged from early infancy to 13 years, from 8 cohorts of European ancestry. We found a positive association between additional minor (A) alleles and BMI from 5.5 years onwards, but an inverse association below age 2.5 years. Modelling median BMI curves for each genotype using the LMS method, we found that carriers of minor alleles showed lower BMI in infancy, earlier adiposity rebound (AR), and higher BMI later in childhood. Differences by allele were consistent with two independent processes: earlier AR equivalent to accelerating developmental age by 2.37% (95% CI 1.87, 2.87, p?=?10(-20)) per A allele and a positive age by genotype interaction such that BMI increased faster with age (p?=?10(-23)). We also fitted a linear mixed effects model to relate genotype to the BMI curve inflection points adiposity peak (AP) in infancy and AR. Carriage of two minor alleles at rs9939609 was associated with lower BMI at AP (-0.40% (95% CI: -0.74, -0.06), p?=?0.02), higher BMI at AR (0.93% (95% CI: 0.22, 1.64), p?=?0.01), and earlier AR (-4.72% (-5.81, -3.63), p?=?10(-17)), supporting cross-sectional results. Overall, we confirm the expected association between variation at rs9939609 and BMI in childhood, but only after an inverse association between the same variant and BMI in infancy. Patterns are consistent with a shift on the developmental scale, which is reflected in association with the timing of AR rather than just a global increase in BMI. Results provide important information about longitudinal gene effects and about the role of FTO in adiposity. The associated shifts in developmental timing have clinical importance with respect to known relationships between AR and both later-life BMI and metabolic disease risk. 相似文献