全文获取类型
收费全文 | 195篇 |
免费 | 14篇 |
出版年
2022年 | 3篇 |
2021年 | 6篇 |
2020年 | 2篇 |
2018年 | 3篇 |
2017年 | 5篇 |
2016年 | 3篇 |
2015年 | 12篇 |
2014年 | 6篇 |
2013年 | 12篇 |
2012年 | 17篇 |
2011年 | 12篇 |
2010年 | 4篇 |
2009年 | 3篇 |
2008年 | 10篇 |
2007年 | 6篇 |
2006年 | 5篇 |
2005年 | 4篇 |
2004年 | 8篇 |
2003年 | 7篇 |
2002年 | 4篇 |
2001年 | 7篇 |
2000年 | 2篇 |
1999年 | 1篇 |
1996年 | 1篇 |
1994年 | 1篇 |
1992年 | 6篇 |
1991年 | 6篇 |
1990年 | 4篇 |
1989年 | 1篇 |
1988年 | 3篇 |
1987年 | 1篇 |
1986年 | 10篇 |
1985年 | 4篇 |
1984年 | 5篇 |
1983年 | 5篇 |
1981年 | 1篇 |
1980年 | 4篇 |
1979年 | 1篇 |
1978年 | 2篇 |
1977年 | 1篇 |
1976年 | 1篇 |
1971年 | 1篇 |
1970年 | 1篇 |
1969年 | 1篇 |
1968年 | 1篇 |
1967年 | 1篇 |
1965年 | 2篇 |
1960年 | 1篇 |
1959年 | 2篇 |
排序方式: 共有209条查询结果,搜索用时 15 毫秒
41.
Shilpa Bali Sarah Rollauer Pietro Roversi Evelyne Raux‐Deery Susan M. Lea Martin J. Warren Stuart J. Ferguson 《Molecular microbiology》2014,92(1):153-163
It has recently been shown that the biosynthetic route for both the d1‐haem cofactor of dissimilatory cd1 nitrite reductases and haem, via the novel alternative‐haem‐synthesis pathway, involves siroheme as an intermediate, which was previously thought to occur only as a cofactor in assimilatory sulphite/nitrite reductases. In many denitrifiers (which require d1‐haem), the pathway to make siroheme remained to be identified. Here we identify and characterize a sirohydrochlorin–ferrochelatase from Paracoccus pantotrophus that catalyses the last step of siroheme synthesis. It is encoded by a gene annotated as cbiX that was previously assumed to be encoding a cobaltochelatase, acting on sirohydrochlorin. Expressing this chelatase from a plasmid restored the wild‐type phenotype of an Escherichia coli mutant‐strain lacking sirohydrochlorin–ferrochelatase activity, showing that this chelatase can act in the in vivo siroheme synthesis. A ΔcbiX mutant in P. denitrificans was unable to respire anaerobically on nitrate, proving the role of siroheme as a precursor to another cofactor. We report the 1.9 Å crystal structure of this ferrochelatase. In vivo analysis of single amino acid variants of this chelatase suggests that two histidines, His127 and His187, are essential for siroheme synthesis. This CbiX can generally be identified in α‐proteobacteria as the terminal enzyme of siroheme biosynthesis. 相似文献
42.
Muscarinic stimulation of inositol phosphate accumulation and acid secretion in gastric fundic mucosal cells 总被引:1,自引:0,他引:1
The muscarinic agonist, carbachol (CCh), was shown to stimulate the production of inositol phosphates (IP) in isolated cells from rabbit fundic mucosa. This stimulatory effect was time- and dose-dependent: EC50 values for IP1, IP2 and IP3 accumulation were not statistically different. The mean value was 30 +/- 8 microM (n = 6). The corresponding maximal stimulation (% of basal value) observed after 20 min incubation in the presence of 100 microM CCh was 160 +/- 15%. CCh-induced IP accumulation was abolished by atropine (Ki = 0.32 +/- 0.18 nM (n = 3)). The CCh concentrations leading to half-maximal inhibition of N-[3H]methylscopolamine binding and half-maximal IP accumulation were similar. The half-maximal value for CCh-induced aminopyrine accumulation was 8-times lower. These results indicate that IP3-mediated mobilization of intracellular Ca2+ might be involved in CCh-induced acid secretion by parietal cells. 相似文献
43.
44.
Souvik Kar Kiran Kumar Bali Arpita Baisantry Robert Geffers Christian Hartmann Amir Samii Helmut Bertalanffy 《Cellular and molecular neurobiology》2018,38(7):1369-1382
Cerebral cavernous malformations (CCM) are vascular malformations associated with abnormally dilated blood vessels and leaky capillaries that often result in hemorrhages. Despite recent advances, precise understanding of the cellular and molecular mechanism leading to the pathogenesis of CCM remains elusive. Emerging evidence indicates that small nucleolar RNAs (snoRNAs), belonging to the class of non-coding RNAs, may play a significant role as diagnostic markers in human diseases. However, there is no report till date that studied the role of snoRNAs in CCM biology. The objective of the current study was to identify snoRNAs associated with CCM pathogenesis. Using genome-wide small RNA sequencing, we identified a total of 271 snoRNAs reliably expressed in CCM. By applying additional statistical stringency, three snoRNAs (SNORD115-32, SNORD114-22, and SNORD113-3) were found to be significantly downregulated in CCM patient tissue samples (n?=?3) as compared to healthy brains (n?=?3). Deregulation of the selected snoRNAs was further validated by qRT-PCR. Further, cellular localization via in situ hybridization also confirmed robust reduction in the expression of SNORD115-32 and SNORD114-22 in CCM tissues as compared to the healthy controls. By applying high-throughput sequencing and cellular localization analyses, we report here for the first time the genome-wide expression profile of snoRNAs in CCM tissues and a robust downregulation of candidate snoRNAs in CCM conditions. Future studies should warrant the screening in large CCM patient cohorts and will be helpful in the development of potential biomarkers and improved clinical diagnosis. 相似文献
45.
46.
Anastasios I. Darras Vasilios Demopoulos Ioanna Bali Chrysovalanti Tiniakou 《Plant Growth Regulation》2012,68(3):343-350
Of all environmental factors that influence plant growth and development, light and other regions of the electromagnetic spectrum are most essential. In the present study, the effects of ultraviolet-C (UV-C) irradiation on two cultivars, Victor and Glacis, of pot grown geranium (Pelargonium x hortotum) plants were evaluated. Two-year experimental data showed that low doses of UV-C (i.e. 0.5–5.0?kJ?m?2) irradiation led to photomorphogenic changes recorded as increases of fresh and dry weight, number of lateral stems and number of inflorescences formed. Although changes were recorded for both cultivars, responses to UV-C were population dependent with cv. Glacis appearing to be the more responsive one. The number of inflorescences formed on UV-C irradiated cv. Glacis plants was significantly (P?<?0.05) higher to that of the non-irradiated controls throughout the pot trials in 2010 and 2011. For example, in the 2010 pot trial, exposure to 2.5?kJ?m?2 UV-C resulted in the increase of inflorescences by 75?%. Additionally, the number of lateral stems on UV-C irradiated plants of cvs. Victor and Glacis increased by 122?% and 64?%, respectively. Temperatures and PARs during the 2-year pot trials varied to a considerable level and seem to have affected floral development and growth of both cultivars. However, only in cv. Glacis the effect on floral development was significant as cv. Victor geraniums grown in 2010 and 2011 showed comparable numbers of inflorescences. Our results show that brief exposures of geranium plants to UV-C may facilitate the production of high quality final products in a cost effective and environmentally friendly way. 相似文献
47.
Ruth J. Napier Brian A. Norris Alyson Swimm Cynthia R. Giver Wayne A. C. Harris Julie Laval Brooke A. Napier Gopi Patel Ryan Crump Zhenghong Peng William Bornmann Bali Pulendran R. Mark Buller David S. Weiss Rabindra Tirouvanziam Edmund K. Waller Daniel Kalman 《PLoS pathogens》2015,11(3)
Imatinib mesylate (Gleevec) inhibits Abl1, c-Kit, and related protein tyrosine kinases (PTKs) and serves as a therapeutic for chronic myelogenous leukemia and gastrointestinal stromal tumors. Imatinib also has efficacy against various pathogens, including pathogenic mycobacteria, where it decreases bacterial load in mice, albeit at doses below those used for treating cancer. We report that imatinib at such low doses unexpectedly induces differentiation of hematopoietic stem cells and progenitors in the bone marrow, augments myelopoiesis but not lymphopoiesis, and increases numbers of myeloid cells in blood and spleen. Whereas progenitor differentiation relies on partial inhibition of c-Kit by imatinib, lineage commitment depends upon inhibition of other PTKs. Thus, imatinib mimics “emergency hematopoiesis,” a physiological innate immune response to infection. Increasing neutrophil numbers by adoptive transfer sufficed to reduce mycobacterial load, and imatinib reduced bacterial load of Franciscella spp., which do not utilize imatinib-sensitive PTKs for pathogenesis. Thus, potentiation of the immune response by imatinib at low doses may facilitate clearance of diverse microbial pathogens. 相似文献
48.
Construction of a genetic linkage map and mapping of drought tolerance trait in Indian beveragial tea 总被引:1,自引:0,他引:1
49.
ERK1-/- mice exhibit Th1 cell polarization and increased susceptibility to experimental autoimmune encephalomyelitis 总被引:2,自引:0,他引:2
Agrawal A Dillon S Denning TL Pulendran B 《Journal of immunology (Baltimore, Md. : 1950)》2006,176(10):5788-5796
Activation of MAPK ERK1/2 has been shown to play an important role in Th1/Th2 polarization and in regulating cytokine production from APCs. The ERK family consists of two members ERK1 and ERK2, which share approximately 84% identity at the amino acid level and can compensate for each other for most functions. Despite these features, ERK1 and ERK2 do serve different functions, but there is very little information on the contribution of individual forms of ERK on innate and adaptive immune responses. In this study, we describe that ERK1(-/-) mice display a bias toward Th1 type immune response. Consistent with this observation, dendritic cells from ERK1(-/-) mice show enhanced IL-12p70 and reduced IL-10 secretion in response to TLR stimulation. Furthermore, serum from ERK1(-/-) mice had 100-fold higher total IgG2b and 10-fold higher total IgG2a and IgG1 Ab isotype titers, and enhanced levels of Ag-specific IgG2b Ab titers, compared with wild-type mice. Consistent with this enhanced Th1 bias, ERK1(-/-) mice showed enhanced susceptibility to myelin oligodendrocyte glycoprotein (MOG)35-55 peptide-induced experimental autoimmune encephalomyelitis (EAE) and developed EAE earlier, and with increased severity, compared with wild-type mice. Importantly, there was a profound skewing toward Th1 responses in ERK1(-/-) mice, with higher IFN-gamma production and lower IL-5 production in MOG35-55-primed T cells, as well as an augmentation in the MOG-specific IgG2a and IgG2b Th1 Ab isotypes. Finally, increased infiltrating cells and myelin destruction was observed in the spinal cord of ERK1(-/-) mice. Taken together, our data suggest that deficiency of ERK1 biases the immune response toward Th1 resulting in increased susceptibility to EAE. 相似文献
50.
Nicole Remy-Heintz Richard Magous Jean-Pierre Bali 《Biochemical and biophysical research communications》1980,93(4):1217-1224
The labelling of α1-acid glycoprotein (AGP) with (3H)-sodium borohydride was compared to the labelling with (125I)-sodium iodide by the chloramine T method in view to its use in a radioimmunoassay. The tritium labelling allowed to reach a high specific radioactivity similar to that obtained with iodide ((3H)-AGP: 29.8 mCi/mg; (125I)-AGP: 30.5 mCi/mg). Each mole of sialic acid residue of AGP contains one atom of tritium. The stability of (3H)-AGP was better than that of (125I)-AGP as indicated by its immunoreactivity as a function of time. Immunoreactivities and standard curves were similar for the two tracers but affinity of antiserum was higher for (125I)-AGP than for (3H)-AGP. Tritium labelling by (3H)-borohydride will be very useful for glycoprotein antigens which cannot be labelled with (125I)-iodide. 相似文献