全文获取类型
收费全文 | 400篇 |
免费 | 41篇 |
出版年
2021年 | 5篇 |
2019年 | 7篇 |
2018年 | 5篇 |
2017年 | 6篇 |
2016年 | 3篇 |
2015年 | 15篇 |
2014年 | 14篇 |
2013年 | 18篇 |
2012年 | 19篇 |
2011年 | 17篇 |
2010年 | 6篇 |
2009年 | 11篇 |
2008年 | 11篇 |
2007年 | 10篇 |
2006年 | 15篇 |
2005年 | 11篇 |
2004年 | 9篇 |
2003年 | 19篇 |
2002年 | 11篇 |
2001年 | 10篇 |
2000年 | 11篇 |
1999年 | 8篇 |
1998年 | 6篇 |
1997年 | 7篇 |
1995年 | 6篇 |
1992年 | 6篇 |
1991年 | 8篇 |
1990年 | 9篇 |
1989年 | 8篇 |
1988年 | 8篇 |
1987年 | 6篇 |
1986年 | 12篇 |
1985年 | 13篇 |
1984年 | 6篇 |
1983年 | 5篇 |
1982年 | 4篇 |
1981年 | 8篇 |
1980年 | 5篇 |
1979年 | 8篇 |
1978年 | 7篇 |
1976年 | 3篇 |
1975年 | 10篇 |
1974年 | 5篇 |
1970年 | 6篇 |
1969年 | 3篇 |
1968年 | 5篇 |
1966年 | 4篇 |
1965年 | 2篇 |
1963年 | 2篇 |
1961年 | 7篇 |
排序方式: 共有441条查询结果,搜索用时 22 毫秒
21.
HeLa cells were synchronized with a double thymidine block. Ribosomal subunits, monomers and polyribosomes have been quantitatively analysed at hourly intervals, during interphase, and every 15 min, during mitosis. This analysis was performed on linear 7-47% sucrose gradients. From the beginning of G1 up to the end of S phase, a certain equilibrium among ribosomal subunits, monomers and polyribosomes is maintained, while from the time of entering G2 to M the translation machinery appears to be mobilized in the sense of polysome formation. Under these conditions, the amount of polysomes per cell during the mitotic cycle is expressed by a bi-phasic pattern showing pre- and post-mitotic peaks with a falling-off during S. The G1 peak, meanwhile, is much lower than the G2 peak. The incorporation of [3H]leucine into nascent polypeptide chains on polysomes, as well as into bulk cell proteins and into nuclear and cytoplasmic proteins considered separately, is also represented by a bi-phasic curve which shows, however, a higher peak in G1 and a lower peak in G2, with two fallings-off during S and M, respectively. Since between the G1 and the G2 amino acid pools there are not strong differences of leucine concentration, the discrepancy between the amount of polysomes and the rate of labelling is discussed on the basis of the differences of polysome shape found at the different stages of the cycle. In young cells, in fact, there is an abundance of small polysomes, while in the old cell large polysomes predominate. It is suggested that, in the old cell, the rate of translation on large polysomes could be relatively lower or that among these heavy aggregates a given number of "frozen" polysomes could be present. The ribosome state is considered as a probable limiting-factor of translation, particularly in mitosis. 相似文献
22.
23.
Alexander Woglar Anahita Daryabeigi Adele Adamo Cornelia Habacher Thomas Machacek Adriana La Volpe Verena Jantsch 《PLoS genetics》2013,9(3)
Faithful chromosome segregation during meiosis I depends on the establishment of a crossover between homologous chromosomes. This requires induction of DNA double-strand breaks (DSBs), alignment of homologs, homolog association by synapsis, and repair of DSBs via homologous recombination. The success of these events requires coordination between chromosomal events and meiotic progression. The conserved SUN/KASH nuclear envelope bridge establishes transient linkages between chromosome ends and cytoskeletal forces during meiosis. In Caenorhabditis elegans, this bridge is essential for bringing homologs together and preventing nonhomologous synapsis. Chromosome movement takes place during synapsis and recombination. Concomitant with the onset of chromosome movement, SUN-1 clusters at chromosome ends associated with the nuclear envelope, and it is phosphorylated in a chk-2- and plk-2-dependent manner. Identification of all SUN-1 phosphomodifications at its nuclear N terminus allowed us to address their role in prophase I. Failures in recombination and synapsis led to persistent phosphorylations, which are required to elicit a delay in progression. Unfinished meiotic tasks elicited sustained recruitment of PLK-2 to chromosome ends in a SUN-1 phosphorylation–dependent manner that is required for continued chromosome movement and characteristic of a zygotene arrest. Furthermore, SUN-1 phosphorylation supported efficient synapsis. We propose that signals emanating from a failure to successfully finish meiotic tasks are integrated at the nuclear periphery to regulate chromosome end–led movement and meiotic progression. The single unsynapsed X chromosome in male meiosis is precluded from inducing a progression delay, and we found it was devoid of a population of phosphorylated SUN-1. This suggests that SUN-1 phosphorylation is critical to delaying meiosis in response to perturbed synapsis. SUN-1 may be an integral part of a checkpoint system to monitor establishment of the obligate crossover, inducible only in leptotene/zygotene. Unrepaired DSBs and unsynapsed chromosomes maintain this checkpoint, but a crossover intermediate is necessary to shut it down. 相似文献
24.
Terry G. Coursey Niral B. Gandhi Eugene A. Volpe Stephen C. Pflugfelder Cintia S. de Paiva 《PloS one》2013,8(11)
CD4+ T cells are essential to pathogenesis of ocular surface disease in dry eye. Two subtypes of CD4+ T cells, Th1 and Th17 cells, function concurrently in dry eye to mediate disease. This occurs in spite of the cross-regulation of IFN-γ and IL-17A, the prototypical cytokines Th1 and Th17 cells, respectively. Essential to an effective immune response are chemokines that direct and summon lymphocytes to specific tissues. T cell trafficking has been extensively studied in other models, but this is the first study to examine the role of chemokine receptors in ocular immune responses. Here, we demonstrate that the chemokine receptors, CCR6 and CXCR3, which are expressed on Th17 and Th1 cells, respectively, are required for the pathogenesis of dry eye disease, as CCR6KO and CXCR3KO mice do not develop disease under desiccating stress. CD4+ T cells from CCR6KO and CXCR3KO mice exposed to desiccating stress (DS) do not migrate to the ocular surface, but remain in the superficial cervical lymph nodes. In agreement with this, CD4+ T cells from CCR6 and CXCR3 deficient donors exposed to DS, when adoptively transferred to T cell deficient recipients manifest minimal signs of dry eye disease, including significantly less T cell infiltration, goblet cell loss, and expression of inflammatory cytokine and matrix metalloproteinase expression compared to wild-type donors. These findings highlight the important interaction of chemokine receptors on T cells and chemokine ligand expression on epithelial cells of the cornea and conjunctiva in dry eye pathogenesis and reveal potential new therapeutic targets for dry eye disease. 相似文献
25.
Haiyan Chen Giorgia Valle Sandra Furlan Alma Nani Sandor Gyorke Michael Fill Pompeo Volpe 《The Journal of general physiology》2013,142(2):127-136
Release of Ca2+ from the sarcoplasmic reticulum (SR) drives contractile function of cardiac myocytes. Luminal Ca2+ regulation of SR Ca2+ release is fundamental not only in physiology but also in physiopathology because abnormal luminal Ca2+ regulation is known to lead to arrhythmias, catecholaminergic polymorphic ventricular tachycardia (CPVT), and/or sudden cardiac arrest, as inferred from animal model studies. Luminal Ca2+ regulates ryanodine receptor (RyR)2-mediated SR Ca2+ release through mechanisms localized inside the SR; one of these involves luminal Ca2+ interacting with calsequestrin (CASQ), triadin, and/or junctin to regulate RyR2 function.CASQ2-RyR2 regulation was examined at the single RyR2 channel level. Single RyR2s were incorporated into planar lipid bilayers by the fusion of native SR vesicles isolated from either wild-type (WT), CASQ2 knockout (KO), or R33Q-CASQ2 knock-in (KI) mice. KO and KI mice have CPVT-like phenotypes. We show that CASQ2(WT) action on RyR2 function (either activation or inhibition) was strongly influenced by the presence of cytosolic MgATP. Function of the reconstituted CASQ2(WT)–RyR2 complex was unaffected by changes in luminal free [Ca2+] (from 0.1 to 1 mM). The inhibition exerted by CASQ2(WT) association with the RyR2 determined a reduction in cytosolic Ca2+ activation sensitivity. RyR2s from KO mice were significantly more sensitive to cytosolic Ca2+ activation and had significantly longer mean open times than RyR2s from WT mice. Sensitivity of RyR2s from KI mice was in between that of RyR2 channels from KO and WT mice. Enhanced cytosolic RyR2 Ca2+ sensitivity and longer RyR2 open times likely explain the CPVT-like phenotype of both KO and KI mice. 相似文献
26.
27.
Anthony P. Clevenger John Paczkowski John P. Volpe Jason T. Fisher 《Ecology and evolution》2016,6(5):1493-1503
Understanding a species’ behavioral response to rapid environmental change is an ongoing challenge in modern conservation. Anthropogenic landscape modification, or “human footprint,” is well documented as a central cause of large mammal decline and range contractions where the proximal mechanisms of decline are often contentious. Direct mortality is an obvious cause; alternatively, human‐modified landscapes perceived as unsuitable by some species may contribute to shifts in space use through preferential habitat selection. A useful approach to tease these effects apart is to determine whether behaviors potentially associated with risk vary with human footprint. We hypothesized wolverine (Gulo gulo) behaviors vary with different degrees of human footprint. We quantified metrics of behavior, which we assumed to indicate risk perception, from photographic images from a large existing camera‐trapping dataset collected to understand wolverine distribution in the Rocky Mountains of Alberta, Canada. We systematically deployed 164 camera sites across three study areas covering approximately 24,000 km2, sampled monthly between December and April (2007–2013). Wolverine behavior varied markedly across the study areas. Variation in behavior decreased with increasing human footprint. Increasing human footprint may constrain potential variation in behavior, through either restricting behavioral plasticity or individual variation in areas of high human impact. We hypothesize that behavioral constraints may indicate an increase in perceived risk in human‐modified landscapes. Although survival is obviously a key contributor to species population decline and range loss, behavior may also make a significant contribution. 相似文献
28.
Giulia Schiroli Anastasia Conti Samuele Ferrari Lucrezia della Volpe Aurelien Jacob Luisa Albano Stefano Beretta Andrea Calabria Valentina Vavassori Patrizia Gasparini Eralda Salataj Delphine Ndiaye-Lobry Chiara Brombin Julie Chaumeil Eugenio Montini Ivan Merelli Pietro Genovese Luigi Naldini Raffaella Di Micco 《Cell Stem Cell》2019,24(4):551-565.e8
29.
30.
Dalla Serra M Fagiuoli G Nordera P Bernhart I Della Volpe C Di Giorgio D Ballio A Menestrina G 《Molecular plant-microbe interactions : MPMI》1999,12(5):391-400
Pseudomonas syringae pv. syringae produces two groups of cyclic lipodepsipeptides (LDPs): the nona-peptides syringomycins, syringostatins, and syringotoxin (ST), and the more complex syringopeptins composed of either 22 or 25 amino acid residues (SP22 and SP25). Both classes of peptides significantly contribute to bacterial pathogenesis and their primary target of action seems to be the plasma membrane. We studied and compared the activity of some members of these two classes of LDPs on red blood cells and on model membranes (monolayers and unilamellar vesicles). All peptides induced red blood cell hemolysis. The mechanism was apparently that of a colloid-osmotic shock caused by the formation of pores, as it could be prevented by osmoticants of adequate size. Application of the Renkin equation indicated a radius of approximately 1 nm for the lesions formed by syringopeptins SP22A and SP25A, whereas those formed by syringomycin E (SRE) had a variable, dose-dependent size ranging from 0.7 up to 1.7 nm. All tested LDPs displayed surface activity, forming peptide monolayers with average molecular areas of 1.2 nm2 (SRE), 1.5 nm2 (SP22A), and 1.3 nm2 (SP25A). They also partitioned into preformed lipid monolayers occupying molecular areas that ranged from 0.6 to 1.7 nm2 depending on the peptide and the lipid composition of the film. These LDPs formed channels in lipid vesicles as indicated by the release of an entrapped fluorescent dye (calcein). The extent of permeabilization was dependent on the concentration of the peptide and the composition of the lipid vesicles, with a preference for those containing a sterol. From the dose dependence of the permeabilization it was inferred that LDPs increased membrane permeability by forming oligomeric channels containing from four to seven monomers. On average, syringopeptin oligomers were smaller than SRE and ST oligomers. 相似文献