全文获取类型
收费全文 | 76篇 |
免费 | 15篇 |
专业分类
91篇 |
出版年
2017年 | 1篇 |
2015年 | 1篇 |
2014年 | 3篇 |
2013年 | 4篇 |
2012年 | 2篇 |
2011年 | 5篇 |
2010年 | 2篇 |
2009年 | 4篇 |
2008年 | 4篇 |
2007年 | 4篇 |
2006年 | 2篇 |
2005年 | 2篇 |
2004年 | 2篇 |
2003年 | 3篇 |
2002年 | 1篇 |
2001年 | 4篇 |
2000年 | 3篇 |
1999年 | 2篇 |
1998年 | 5篇 |
1997年 | 3篇 |
1996年 | 4篇 |
1995年 | 1篇 |
1994年 | 2篇 |
1992年 | 1篇 |
1991年 | 3篇 |
1990年 | 1篇 |
1989年 | 4篇 |
1988年 | 4篇 |
1987年 | 3篇 |
1986年 | 2篇 |
1985年 | 1篇 |
1984年 | 1篇 |
1983年 | 1篇 |
1982年 | 2篇 |
1981年 | 1篇 |
1975年 | 1篇 |
1971年 | 1篇 |
1968年 | 1篇 |
排序方式: 共有91条查询结果,搜索用时 0 毫秒
11.
Characterization of terminal NeuNAcalpha2-3Galbeta1-4GlcNAc sequence in lipooligosaccharides of Neisseria meningitidis 总被引:1,自引:0,他引:1
Group B and C Neisseria meningitidis are the major cause of meningococcal
disease in the United States and in Europe. N . meningitidis
lipooligosaccharide (LOS), a major surface antigen, can be divided into 12
immunotypes of which L1 through L8 were found among Group B and C
organisms. Groups B and C but not Group A may sialylate their LOSs with
N-acetylneuraminic acid (NeuNAc) at the nonreducing end because they
synthesize CMP-NeuNAc. Using sialic acid-galactose binding lectins as
probes in an ELISA format, six of the eight LOS immunotypes (L2, L3, L4,
L5, L7, and L8) in Groups B and C bound specifically to Maackia amurensis
leukoagglutinin (MAL), which recognizes NeuNAcalpha2- 3Galbeta1-4GlcNAc/Glc
sequence, but not to Sambucus nigra agglutinin, which binds
NeuNAcalpha2-6Gal sequence. The combination of SDS-PAGE and MAL-blot
analyses revealed that these six LOSs contained only the
NeuNAcalpha2-3Galbeta1-4GlcNAc trisaccharide sequence in their 4.1 kDa LOS
components, which have a common terminal lacto-N-neotetraose (LNnT,
Galbeta1-4GlcNAcbeta1-3Galbeta1-4Glc) structure when nonsialylated as shown
by previous studies. The LOS-lectin binding was abolished when the LOSs
were treated with Newcastle disease viral neuraminidase which cleaves
alpha2-->3 linked sialic acid. Methylation analysis of a representative
LOS (L2) confirmed that NeuNAc is 2-->3 linked to Gal. Thus, these LOSs
structurally mimic certain glycolipids, i.e., paragloboside (LNnT-ceramide)
and sialylparagloboside and some glycoproteins in having LNnT and
N-acetyllactosamine sequences, respectively, with or without alpha2-->3
linked NeuNAc. The molecular mimicry of the LOSs may play a role in the
pathogenesis of N.meningitidis by assisting the organism to evade host
immune defenses in man.
相似文献
12.
Forli F Passetti S Mancuso M Seccia V Siciliano G Nesti C Berrettini S 《Bioscience reports》2007,27(1-3):113-123
Mitochondrial diseases (MD) are a clinically heterogeneous group of disorders that arise as a result of dysfunction of the
mitochondrial respiratory chain. Sensorineural hearing loss (SNHL) is often associated to mitochondrial dysfunctions both
in syndromic, nonsyndromic forms. SNHL has been described in association to different mitochondrial multisystemic syndromes,
often characterized by an important neuromuscular involvement. Because of the clinical relevance of the associated neurological
symptoms, the occurrence of SNHL is often underestimated and undiagnosed. In this study we evaluated the incidence of SNHL
in a group of 17 patients with MD. We detected some degree of hearing impairment in 8/17 patients (47%), thus confirming the
frequency of hearing impairment in MD. Furthermore, we want to highlight the role of the audiologist and otolaryngologist
in the diagnosis and characterization of a MD, which should be suspected in all the cases in which the hearing loss is associated
to signs and symptoms characteristic of mitochondrial dysfunction, especially if the family history is positive for hearing
loss or MD in the maternal line. 相似文献
13.
Clarke TK Ambrose-Lanci L Ferraro TN Berrettini WH Kampman KM Dackis CA Pettinati HM O'Brien CP Oslin DW Lohoff FW 《Genes, Brain & Behavior》2012,11(4):415-423
Genetic factors are believed to account for 30-50% of the risk for cocaine and heroin addiction. Dynorphin peptides, derived from the prodynorphin (PDYN) precursor, bind to opioid receptors, preferentially the kappa-opioid receptor, and may mediate the aversive effects of drugs of abuse. Dynorphin peptides produce place aversion in animals and produce dysphoria in humans. Cocaine and heroin have both been shown to increase expression of PDYN in brain regions relevant for drug reward and use. Polymorphisms in PDYN are therefore hypothesized to increase risk for addiction to drugs of abuse. In this study, 3 polymorphisms in PDYN (rs1022563, rs910080 and rs1997794) were genotyped in opioid-addicted [248 African Americans (AAs) and 1040 European Americans (EAs)], cocaine-addicted (1248 AAs and 336 EAs) and control individuals (674 AAs and 656 EAs). Sex-specific analyses were also performed as a previous study identified PDYN polymorphisms to be more significantly associated with female opioid addicts. We found rs1022563 to be significantly associated with opioid addiction in EAs [P = 0.03, odds ratio (OR) = 1.31; false discovery rate (FDR) corrected q-value]; however, when we performed female-specific association analyses, the OR increased from 1.31 to 1.51. Increased ORs were observed for rs910080 and rs199774 in female opioid addicts also in EAs. No statistically significant associations were observed with cocaine or opioid addiction in AAs. These data show that polymorphisms in PDYN are associated with opioid addiction in EAs and provide further evidence that these risk variants may be more relevant in females. 相似文献
14.
Fine mapping of a seizure susceptibility locus on mouse Chromosome 1: nomination of Kcnj10 as a causative gene 总被引:2,自引:2,他引:0
Thomas N. Ferraro Gregory T. Golden George G. Smith James F. Martin Falk W. Lohoff Tracy A. Gieringer Deborah Zamboni Candice L. Schwebel Danielle M. Press Stephanie Hongyu O. KratzerZhao Wade H. Berrettini Russell J. Buono 《Mammalian genome》2004,15(4):239-251
Previous quantitative trait loci (QTL) mapping studies document that the distal region of mouse Chromosome (Chr) 1 contains a gene(s) that is in large part responsible for the difference in seizure susceptibility between C57BL/6 (B6) (relatively seizure-resistant) and DBA/2 (D2) (relatively seizure-sensitive) mice. We now confirm this seizure-related QTL (Szs1) using reciprocal, interval-specific congenic strains and map it to a 6.6-Mb segment between Pbx1 and D1Mit150. Haplotype conservation between strains within this segment suggests that Szs1 may be localized more precisely to a 4.1-Mb critical interval between Fcgr3 and D1Mit150. We compared the coding region sequences of candidate genes between B6 and D2 mice using RT-PCR, amplification from genomic DNA, and database searching and discovered 12 brain-expressed genes with SNPs that predict a protein amino acid variation. Of these, the most compelling seizure susceptibility candidate is Kcnj10. A survey of the Kcnj10 SNP among other inbred mouse strains revealed a significant effect on seizure sensitivity such that most strains possessing a haplotype containing the B6 variant of Kcnj10 have higher seizure thresholds than those strains possessing the D2 variant. The unique role of inward-rectifying potassium ion channels in membrane physiology coupled with previous strong association between ion channel gene mutations and seizure phenotypes puts even greater focus on Kcnj10 in the present model. In summary, we confirmed a seizure-related QTL of large effect on mouse Chr 1 and mapped it to a finely delimited region. The critical interval contains several candidate genes, one of which, Kcnj10, exhibits a potentially important polymorphism with regard to fundamental aspects of seizure susceptibility. 相似文献
15.
G G Nenci M Berrettini P Parise G Agnelli 《Folia haematologica (Leipzig, Germany : 1928)》1982,109(3):453-463
A case of systemic mastocytosis with lymphatic, digestive, nervous and bone involvement and with persistent heparinaemia is described. The true heparin nature of the circulating anticoagulant was proved by the conventional titrimetric method with protamine sulphate and by the new specific amidolytic assay of its Xa-inhibiting properties. This human circulating heparin displayed a low specific activity as expressed by its activity/weight ratio. 相似文献
16.
17.
Michael CW Chan Renee WY Chan Wendy CL Yu Carol CC Ho WH Chui CK Lo Kit M Yuen Yi Guan John M Nicholls JS Malik Peiris 《Respiratory research》2009,10(1):102
Background
Highly pathogenic avian influenza (HPAI) H5N1 virus is entrenched in poultry in Asia and Africa and continues to infect humans zoonotically causing acute respiratory disease syndrome and death. There is evidence that the virus may sometimes spread beyond respiratory tract to cause disseminated infection. The primary target cell for HPAI H5N1 virus in human lung is the alveolar epithelial cell. Alveolar epithelium and its adjacent lung microvascular endothelium form host barriers to the initiation of infection and dissemination of influenza H5N1 infection in humans. These are polarized cells and the polarity of influenza virus entry and egress as well as the secretion of cytokines and chemokines from the virus infected cells are likely to be central to the pathogenesis of human H5N1 disease.Aim
To study influenza A (H5N1) virus replication and host innate immune responses in polarized primary human alveolar epithelial cells and lung microvascular endothelial cells and its relevance to the pathogenesis of human H5N1 disease.Methods
We use an in vitro model of polarized primary human alveolar epithelial cells and lung microvascular endothelial cells grown in transwell culture inserts to compare infection with influenza A subtype H1N1 and H5N1 viruses via the apical or basolateral surfaces.Results
We demonstrate that both influenza H1N1 and H5N1 viruses efficiently infect alveolar epithelial cells from both apical and basolateral surface of the epithelium but release of newly formed virus is mainly from the apical side of the epithelium. In contrast, influenza H5N1 virus, but not H1N1 virus, efficiently infected polarized microvascular endothelial cells from both apical and basolateral aspects. This provides a mechanistic explanation for how H5N1 virus may infect the lung from systemic circulation. Epidemiological evidence has implicated ingestion of virus-contaminated foods as the source of infection in some instances and our data suggests that viremia, secondary to, for example, gastro-intestinal infection, can potentially lead to infection of the lung. HPAI H5N1 virus was a more potent inducer of cytokines (e.g. IP-10, RANTES, IL-6) in comparison to H1N1 virus in alveolar epithelial cells, and these virus-induced chemokines were secreted onto both the apical and basolateral aspects of the polarized alveolar epithelium.Conclusion
The predilection of viruses for different routes of entry and egress from the infected cell is important in understanding the pathogenesis of influenza H5N1 infection and may help unravel the pathogenesis of human H5N1 disease. 相似文献18.
Background
Concurrent peptide fragmentation (i.e. shotgun CID, parallel CID or MSE) has emerged as an alternative to data-dependent acquisition in generating peptide fragmentation data in LC-MS/MS proteomics experiments. Concurrent peptide fragmentation data acquisition has been shown to be advantageous over data-dependent acquisition by providing greater detection dynamic range and providing more accurate quantitative information. Nevertheless, concurrent peptide fragmentation data acquisition remains to be widely adopted due to the lack of published algorithms designed specifically to process or interpret such data acquired on any mass spectrometer. 相似文献19.
T. N. Ferraro G. T. Golden G. G. Smith N. J. Schork P. St. Jean C. Ballas H. Choi W. H. Berrettini 《Mammalian genome》1997,8(3):200-208
Mature DBA/2J (D2) mice are very sensitive to seizures induced by various chemical and physical stimuli, whereas C57BL/6J
(B6) mice are relatively seizure resistant. We have conducted a genome-wide search for quantitative trait loci (QTLs) influencing
the differential sensitivity of these strains to kainic acid (KA)-induced seizures by studying an F2 intercross population. Parental, F1, and F2 mice (8–10 weeks of age) were injected subcutaneously with 25 mg/kg of KA and observed for 3 h. Latencies to focal and generalized
seizures and status epilepticus were recorded and used to calculate an overall seizure score. Results of seizure testing indicated
that the difference in susceptibility to KA-induced seizures between D2 and B6 mice is a polygenic phenomenon with at least
65% of the variance due to genetic factors. First-pass genome screening (10-cM marker intervals) in F2 progeny (n = 257) documented a QTL of moderate effect on Chromosome (Chr) 1 with a peak LOD score of 5.5 (17% of genetic
variance explained) localized between D1Mit30 and D1Mit16. Provisional QTLs of small effect were detected on Chr 11 (D11Mit224–D11Mit14), 15 (D15Mit6–D15Mit46) and 18 (D18Mit9–D18Mit144). Multiple locus models generally confirmed the Mapmaker/QTL results and also provided evidence for another QTL on Chr 4
(D4Mit9). Multilocus analysis of seizure severity suggested that additional loci on Chrs 5 (D5Mit11), 7 (D7Mit66), and 15 (D15Nds2) might also contribute to KA-induced seizure response. Overall, our results document a complex genetic determinism for KA-induced
seizures in these mouse strains with contributions from as many as eight QTLs.
Received: 16 April 1996 / Accepted: 21 October 1996 相似文献
20.
Statistical analyses of DNA sequences of globin genes (beta A, beta C, and
gamma) from goat and sheep (including new sequence information for the
second intron of sheep beta A and gamma, kindly provided by A. Davis and A.
W. Nienhuis) indicate that the rates of nonsynonymous substitution in these
genes have been greatly accelerated following the gene duplication
separating gamma and the ancestor of beta A and beta C and the gene
duplication separating beta A and beta C. In both cases the acceleration
was apparently due to relaxation of purifying selection (functional
constraints) rather than advantageous mutations because acceleration
occurred only in less important parts of the beta globin chain. The rates
of nonsynonymous substitution in these genes are estimated to be about 2.3
x 10(-9) per site per year, which is three times higher than that for the
divergence between human beta and mouse beta major globin genes. Our
analyses further suggest that the rate of synonymous substitution in
functional genes and the rate of substitution in pseudogenes are
approximately equal and are between 2.8 x 10(-9) and 5.0 x 10(-9) and that
the rate of substitution in introns is about 3.0 x 10(-9). The divergence
time between beta A and beta C and that between gamma and the beta A-beta C
pair are about 12 and 30 million years, respectively. The proportion of
transition mutations is estimated to be 64%, two times higher than expected
under random mutation but considerably lower than the 96% estimated for
animal mitochondrial DNA.
相似文献