全文获取类型
收费全文 | 228篇 |
免费 | 54篇 |
出版年
2022年 | 3篇 |
2021年 | 2篇 |
2020年 | 3篇 |
2019年 | 3篇 |
2017年 | 5篇 |
2016年 | 7篇 |
2015年 | 10篇 |
2014年 | 13篇 |
2013年 | 14篇 |
2012年 | 19篇 |
2011年 | 10篇 |
2010年 | 16篇 |
2009年 | 10篇 |
2008年 | 12篇 |
2007年 | 11篇 |
2006年 | 12篇 |
2005年 | 15篇 |
2004年 | 16篇 |
2003年 | 6篇 |
2002年 | 8篇 |
2001年 | 16篇 |
2000年 | 9篇 |
1999年 | 7篇 |
1998年 | 6篇 |
1997年 | 1篇 |
1996年 | 5篇 |
1995年 | 3篇 |
1994年 | 2篇 |
1993年 | 6篇 |
1992年 | 7篇 |
1991年 | 6篇 |
1990年 | 1篇 |
1989年 | 2篇 |
1988年 | 3篇 |
1987年 | 1篇 |
1986年 | 1篇 |
1985年 | 3篇 |
1984年 | 3篇 |
1982年 | 1篇 |
1981年 | 1篇 |
1979年 | 1篇 |
1973年 | 1篇 |
1929年 | 1篇 |
排序方式: 共有282条查询结果,搜索用时 312 毫秒
121.
Liu Y Han N Franchini LF Xu H Pisciottano F Elgoyhen AB Rajan KE Zhang S 《Molecular biology and evolution》2012,29(5):1441-1450
Bats are the only mammals that use highly developed laryngeal echolocation, a sensory mechanism based on the ability to emit laryngeal sounds and interpret the returning echoes to identify objects. Although this capability allows bats to orientate and hunt in complete darkness, endowing them with great survival advantages, the genetic bases underlying the evolution of bat echolocation are still largely unknown. Echolocation requires high-frequency hearing that in mammals is largely dependent on somatic electromotility of outer hair cells. Then, understanding the molecular evolution of outer hair cell genes might help to unravel the evolutionary history of echolocation. In this work, we analyzed the molecular evolution of two key outer hair cell genes: the voltage-gated potassium channel gene KCNQ4 and CHRNA10, the gene encoding the α10 nicotinic acetylcholine receptor subunit. We reconstructed the phylogeny of bats based on KCNQ4 and CHRNA10 protein and nucleotide sequences. A phylogenetic tree built using KCNQ4 amino acid sequences showed that two paraphyletic clades of laryngeal echolocating bats grouped together, with eight shared substitutions among particular lineages. In addition, our analyses indicated that two of these parallel substitutions, M388I and P406S, were probably fixed under positive selection and could have had a strong functional impact on KCNQ4. Moreover, our results indicated that KCNQ4 evolved under positive selection in the ancestral lineage leading to mammals, suggesting that this gene might have been important for the evolution of mammalian hearing. On the other hand, we found that CHRNA10, a gene that evolved adaptively in the mammalian lineage, was under strong purifying selection in bats. Thus, the CHRNA10 amino acid tree did not show echolocating bat monophyly and reproduced the bat species tree. These results suggest that only a subset of hearing genes could underlie the evolution of echolocation. The present work continues to delineate the genetic bases of echolocation and ultrasonic hearing in bats. 相似文献
122.
ALVAC-SIV-gag-pol-env-based vaccination and macaque major histocompatibility complex class I (A*01) delay simian immunodeficiency virus SIVmac-induced immunodeficiency.
下载免费PDF全文
![点击此处可从《Journal of virology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
R Pal D Venzon N L Letvin S Santra D C Montefiori N R Miller E Tryniszewska M G Lewis T C VanCott V Hirsch R Woodward A Gibson M Grace E Dobratz P D Markham Z Hel J Nacsa M Klein J Tartaglia G Franchini 《Journal of virology》2002,76(1):292-302
T-cell-mediated immune effector mechanisms play an important role in the containment of human immunodeficiency virus/simian immunodeficiency virus (HIV/SIV) replication after infection. Both vaccination- and infection-induced T-cell responses are dependent on the host major histocompatibility complex classes I and II (MHC-I and MHC-II) antigens. Here we report that both inherent, host-dependent immune responses to SIVmac251 infection and vaccination-induced immune responses to viral antigens were able to reduce virus replication and/or CD4+ T-cell loss. Both the presence of the MHC-I Mamu-A*01 genotype and vaccination of rhesus macaques with ALVAC-SIV-gag-pol-env (ALVAC-SIV-gpe) contributed to the restriction of SIVmac251 replication during primary infection, preservation of CD4+ T cells, and delayed disease progression following intrarectal challenge exposure of the animals to SIV(mac251 (561)). ALVAC-SIV-gpe immunization induced cytotoxic T-lymphocyte (CTL) responses cumulatively in 67% of the immunized animals. Following viral challenge, a significant secondary virus-specific CD8+ T-cell response was observed in the vaccinated macaques. In the same immunized macaques, a decrease in virus load during primary infection (P = 0.0078) and protection from CD4 loss during both acute and chronic phases of infection (P = 0.0099 and P = 0.03, respectively) were observed. A trend for enhanced survival of the vaccinated macaques was also observed. Neither boosting the ALVAC-SIV-gpe with gp120 immunizations nor administering the vaccine by the combination of mucosal and systemic immunization routes increased significantly the protective effect of the ALVAC-SIV-gpe vaccine. While assessing the role of MHC-I Mamu-A*01 alone in the restriction of viremia following challenge of nonvaccinated animals with other SIV isolates, we observed that the virus load was not significantly lower in Mamu-A*01-positive macaques following intravenous challenge with either SIV(mac251 (561)) or SIV(SME660). However, a significant delay in CD4+ T-cell loss was observed in Mamu-A*01-positive macaques in each group. Of interest, in the case of intravenous or intrarectal challenge with the chimeric SIV/HIV strains SHIV(89.6P) or SHIV(KU2), respectively, MHC-I Mamu-A*01-positive macaques did not significantly restrict primary viremia. The finding of the protective effect of the Mamu-A*01 molecule parallels the protective effect of the B*5701 HLA allele in HIV-1-infected humans and needs to be accounted for in the evaluation of vaccine efficacy against SIV challenge models. 相似文献
123.
124.
Carlo Franchini Francesca Chiaia Noja Filomena Corbo Giovanni Lentini Vincenzo Tortorella Alessandro Bartolini Carla Ghelardini Rosanna Matucci Alberto Giotti 《Chirality》1993,5(3):135-142
The antiarrhythmic drug tocainide (5a) and some related chiral α-amino and α-imino anilides (5b–e) were synthesized in optically active form. The antinociceptive effects of the different stereoisomers of these compounds were examined and it was found that the analgesic effect of tocainide is due only to its (?)-(R)-enantiomer. Benzyl replacement for methyl group at the stereogenic centre of tocainide causes loss of activity while both enantiomers of the αiminoxilidide 5e and of the strictly related tocainide analog 5d produce an analgesic effect without any stereoselectivity. Pharmacological tests and [3H] quinuclidinyl benzilate ([3H]QNB) binding assay, taken together, seem to show that the antinociceptive effect of (?)-(R)-tocainide, like the analgesia induced by lidocaine, procaine, and mexiletine, is due to a central presynaptic cholinergic mechanism of action. © 1993 Wiley-Liss, Inc. 相似文献
125.
The p12I, p13II, and p30II proteins encoded by human T-cell leukemia/lymphotropic virus type I open reading frames I and II are localized in three different cellular compartments. 总被引:8,自引:6,他引:2
下载免费PDF全文
![点击此处可从《Journal of virology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Three protein isoforms are encoded by the human T-cell leukemia/lymphotropic virus type I pX region open reading frames (ORF) I and II through alternative splicing. Both the singly and doubly spliced mRNAs from ORF I encode a single 12-kDa protein (p12I), whereas two distinct proteins of 13 kDa (p13II) and 30 kDa (p30II) are encoded from the ORF II alternatively spliced mRNA. Because the p12I protein is very hydrophobic and poorly immunogenic, we genetically engineered its cDNA by adding a short stretch of amino acids from the highly immunogenic epitope HA1 of influenza virus or the AU1 epitope of bovine papillomavirus. The HA1 epitope was also added to the p13II and p30II proteins, albeit rabbit immune sera raised against synthetic peptides were also available. To determine in which cellular compartments these proteins reside, we transfected the tagged and wild-type cDNAs in HeLa/Tat cells and studied their localization by indirect immunofluorescence. The p12I protein was identified in the cellular endomembranes and, particularly, in the perinuclear area. p13II and p30II were found in the nuclei and nucleoli of the transfected cells, respectively. The presence of the HA1 epitope at the carboxy terminus of p13II and p30II did not interfere with their cellular localization, since the rabbit immune sera demonstrated their presence in the same cellular compartments when the untagged proteins were expressed. The defined localization of these proteins in specific cellular compartments warrants further study of their function. 相似文献
126.
Human T-Cell Lymphotropic/Leukemia Virus Type 1 Tax Abrogates p53-Induced Cell Cycle Arrest and Apoptosis through Its CREB/ATF Functional Domain 总被引:18,自引:5,他引:13
下载免费PDF全文
![点击此处可从《Journal of virology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
127.
Human gene (c-fes) related to the onc sequences of Snyder-Theilen feline sarcoma virus. 总被引:6,自引:2,他引:4
下载免费PDF全文
![点击此处可从《Molecular and cellular biology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
G Franchini E P Gelmann R Dalla-Favera R C Gallo F Wong-Staal 《Molecular and cellular biology》1982,2(8):1014-1019
The onc gene (v-fes) of the acutely transforming feline sarcoma virus (Snyder-Theilen strain) has homologous cellular sequences (c-fes) in all vertebrate species, including humans. We isolated from a human DNA library recombinant phages containing overlapping c-fes sequences. The human c-fes locus spans a region of 3.4 kilobases and contains 1.4 kilobases of DNA homologous to the viral onc sequence interspersed with three intervening sequences. 相似文献
128.
Cross-neutralization of human immunodeficiency virus type 1 and 2 and simian immunodeficiency virus isolates. 总被引:4,自引:3,他引:1
下载免费PDF全文
![点击此处可从《Journal of virology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
M Robert-Guroff K Aldrich R Muldoon T L Stern G P Bansal T J Matthews P D Markham R C Gallo G Franchini 《Journal of virology》1992,66(6):3602-3608
In contrast to infrequent and low-titer cross-neutralization of human immunodeficiency virus type 1 (HIV-1) isolates by HIV-2- and simian immunodeficiency virus (SIV)-positive sera, extensive cross-neutralization of HIV-2NIH-Z, SIVMAC251, and SIVAGM208K occurs with high titer, suggesting conservation of epitopes and mechanism(s) of neutralization. The V3 regions of HIV-2 and SIV isolates, minimally related to the HIV-1 homolog, share significant sequence homology and are immunogenic in monkeys as well as in humans. Whereas the crown of the V3 loop is cross-reactive among HIV-1 isolates and elicits neutralizing antibodies of broad specificity, the SIV and especially HIV-2 crown peptides were not well recognized by cross-neutralizing antisera. V3 loop peptides of HIV-2 isolates did not elicit neutralizing antibodies in mice, guinea pigs, or a goat and together with SIV V3 peptides did not inhibit serum neutralization of HIV-2 and SIV. Thus, the V3 loops of HIV-2 and SIV do not appear to constitute simple linear neutralizing epitopes. In view of the immunogenicity of V3 peptides, the failure of conserved crown peptides to react with natural sera implies a significant role of loop conformation in antibody recognition. Our studies suggest that in addition to their grouping by envelope genetic relatedness, HIV-2 and SIV are neutralized similarly to each other but differently from HIV-1. The use of linear peptides of HIV-2 and SIV as immunogens may require greater attention to microconformation, and alternate subunit approaches may be needed in exploiting these viruses as vaccine models. Such approaches may also be applicable to the HIV-1 system in which conformational epitopes, in addition to the V3 loop, participate in virus neutralization. 相似文献
129.
130.
The expression in microglia of two K+ channel populations, inwardly- and delayed outwardly rectifying channels (Kir, Kdr), is under the control of a variety of signals among which inflammatory and immunomodulatory agents. This makes K+ channels good candidates for the control of cell activities and for their adaptation to the changes of the functional state of the cell. Here we investigated on the role played by Kir channels in the control of cytoplasmic Ca2+ movements. In particular, we focused on those linked to nucleotide receptors, which are known to regulate a variety of functions in microglia. By a Fura-2-based video-imaging approach we recorded Ca2+ transients induced by P2 activation. These were composed of an initial peak, mainly due to release from endoplasmic reticulum, and of a long lasting plateau linked to Ca2+ influx through cation non-selective and capacitative channels. In patch-clamp experiments, we observed that Ba2+ (1-100 microM) could inhibit Kir current, but was not effective on Kdr and ATP-induced K+ current. By using Ba2+ as a specific blocker of Kir channels, we found that their inhibition caused a decrease of the Ca2+ level, especially at the end of the 20s long agonist application period. The effect of Ba2+ was mimicked by high K(+)-induced depolarization. We conclude that Kir channels contribute to modulate the amplitude and time course of the ATP-induced Ca2+ transient through the control of membrane potential. We suggest that microglial cells adapt signal transduction mechanisms to the changes of their functional state also by varying the expression and modulating the activity of inwardly rectifying K+ channels. 相似文献