全文获取类型
收费全文 | 190篇 |
免费 | 11篇 |
国内免费 | 1篇 |
出版年
2023年 | 2篇 |
2022年 | 6篇 |
2021年 | 5篇 |
2020年 | 2篇 |
2019年 | 4篇 |
2018年 | 7篇 |
2017年 | 3篇 |
2016年 | 2篇 |
2015年 | 10篇 |
2014年 | 9篇 |
2013年 | 7篇 |
2012年 | 14篇 |
2011年 | 11篇 |
2010年 | 8篇 |
2009年 | 15篇 |
2008年 | 13篇 |
2007年 | 7篇 |
2006年 | 6篇 |
2005年 | 5篇 |
2004年 | 5篇 |
2003年 | 5篇 |
2002年 | 4篇 |
2001年 | 4篇 |
2000年 | 6篇 |
1999年 | 3篇 |
1998年 | 6篇 |
1997年 | 2篇 |
1996年 | 3篇 |
1995年 | 2篇 |
1994年 | 3篇 |
1993年 | 3篇 |
1992年 | 3篇 |
1989年 | 3篇 |
1988年 | 2篇 |
1987年 | 2篇 |
1986年 | 2篇 |
1983年 | 3篇 |
1982年 | 2篇 |
1980年 | 1篇 |
1978年 | 1篇 |
1977年 | 1篇 |
排序方式: 共有202条查询结果,搜索用时 15 毫秒
181.
Schwaiger FW; Weyers E; Buitkamp J; Ede AJ; Crawford A; Epplen JT 《Molecular biology and evolution》1994,11(2):239-249
Exon 2 sequences of an expressed MHC-DRB locus from sheep were examined for
polymorphisms in both the antigen-binding regions and the adjacent intronic
mixed simple tandem repeat. Twenty-one novel exon 2 Ovar-DRB alleles were
identified. Short nucleotide motifs are extensively shared between certain
exon 2 regions of Ovar-DRB alleles. The simple repeat variations, the
number of different amino acids at usually polymorphic sites, and the
number of silent substitutions were reduced in the intraspecies analyses of
sheep DRB sequences, compared with those of cattle and goats. It was
paradoxical that the abundance of different sheep alleles was similar to
that of cattle and goats. This paradox may be explained by postulating a
relatively small number of "ancient" alleles, with the present-day Ovar-DRB
alleles being generated by reciprocal exchange of nucleotide motifs. At the
antigen-binding sites, new combinations of amino acids were maintained in
Ovar-DRB alleles by strong positive selection. In sheep--and less
pronounced in goats and cattle--the DRB alleles can be divided into two
groups. In one group, silent substitutions are increased when compared with
the other. This suggests separate evolutionary pathways for certain groups
of DRB alleles within a species. The simple repetitive sequences are also
discussed with respect to the evolution of DRB alleles.
相似文献
182.
Evolutionary history of the COII/tRNALys intergenic 9 base pair deletion in human mitochondrial DNAs from the Pacific 总被引:14,自引:2,他引:12
Redd AJ; Takezaki N; Sherry ST; McGarvey ST; Sofro AS; Stoneking M 《Molecular biology and evolution》1995,12(4):604-615
Length changes in human mitochondrial DNA (mtDNA) are potentially useful
markers for inferring the evolutionary history of populations. One such
length change is a nine base pair (9-bp) deletion that is located in the
intergenic region between the COII gene and the Lysine tRNA gene
(COII/tRNALys intergenic region). This deletion has been used as a genetic
marker to trace descent from peoples of East Asian origin. A geographic
cline of the deletion frequency across modern Pacific Islander populations
suggests that the deletion may be useful for tracing prehistoric Polynesian
origins and affinities. Mitochondrial DNA sequence variation within two
variable segments of the control region (CR) permits a number of inferences
regarding the evolutionary history of the 9-bp deletion that cannot be
determined from frequency data alone. We obtained CR sequences from 74
mtDNAs with the 9-bp deletion from Indonesia, coastal Papua New Guinea
(PNG), and American Samoa. Phylogenetic and pairwise distribution analysis
of these CR sequences pooled with previously published CR sequences reveals
that the deletion arose independently in Africa and Asia and suggests
possible multiple origins of the deletion in Asia. A clinal increase of the
frequency of the 9-bp deletion across the three Pacific populations is
associated with a decrease in CR sequence diversity, consistent with
founder events. Furthermore, analysis of pairwise difference distributions
indicates an expansion time of proto-Polynesians that began 5,500 yr ago
from Southeast Asia. These results are consistent with the express train
model of Polynesian origins.
相似文献
183.
Antony PB Black Hansha Bhayani Clive AJ Ryder Janet MM Gardner-Medwin Taunton R Southwood 《Arthritis research & therapy》2001,4(3):177
A study was done to determine if the differentiation and activation phenotype of T cells in synovial fluid (SF) from patients with juvenile idiopathic arthritis (JIA) is associated with T-cell proliferation in situ. Mononuclear cells were isolated from 44 paired samples of peripheral blood and SF. Differentiation and activation markers were determined on CD4 and CD8 T cells by flow cytometry. Cell-cycle analysis was performed by propidium iodide staining, and surface-marker expression was also assessed after culture of the T cells under conditions similar to those found in the synovial compartment. The majority of the T cells in the SF were CD45RO+CD45RBdull. There was greater expression of the activation markers CD69, HLA-DR, CD25 and CD71 on T cells from SF than on those from peripheral blood. Actively dividing cells accounted for less than 1% of the total T-cell population in SF. The presence or absence of IL-16 in T-cell cultures with SF or in a hypoxic environment did not affect the expression of markers of T-cell activation. T cells from the SF of patients with JIA were highly differentiated and expressed early and late markers of activation with little evidence of in situ proliferation. This observation refines and extends previous reports of the SF T-cell phenotype in JIA and may have important implications for our understanding of chronic inflammation. 相似文献
184.
Robert A Clayton Colin AJ Dick Alison Mackenzie Michiaki Nagasawa Deirdre Galbraith Stuart F Hastings Simon J MacKenzie 《Respiratory research》2004,5(1):4
BackgroundThe anti-inflammatory effects of the selective phosphodiesterase (PDE) inhibitors cilostazol (PDE 3), RO 20-1724 (PDE 4) and sildenafil (PDE 5) were examined in a murine model of allergic asthma. These compounds were used alone and in combination to determine any potential synergism, with dexamethasone included as a positive control.MethodsControl and ovalbumin sensitised Balb/C mice were administered orally with each of the possible combinations of drugs at a dose of 3 mg/Kg for 10 days.ResultsWhen used alone, RO 20-1724 significantly reduced eosinophil influx into lungs and lowered tumour necrosis factor-α, interleukin-4 and interleukin-5 levels in the bronchoalveolar lavage fluid when compared to untreated mice. Treatment with cilostazol or sildenafil did not significantly inhibit any markers of inflammation measured. Combining any of these PDE inhibitors produced no additive or synergistic effects. Indeed, the anti-inflammatory effects of RO 20-1724 were attenuated by co-administration of either cilostazol or sildenafil.ConclusionsThese results suggest that concurrent treatment with a PDE 3 and/or PDE 5 inhibitor will reduce the anti-inflammatory effectiveness of a PDE 4 inhibitor. 相似文献
185.
Tomasini R Samir AA Pebusque MJ Calvo EL Totaro S Dagorn JC Dusetti NJ Iovanna JL 《European journal of cell biology》2002,81(5):294-301
The mouse stress-induced protein (SIP) mRNA is activated in the pancreas with acute pancreatitis and in several cell lines in response to various stress agents. The SIP gene is alternatively spliced, generating two proteins (SIP'8 and SIP27). Both proteins, located mainly in the nucleus, promote cell death when overexpressed in vitro. We show that induction by stress agents of the expression of SIP18 and SIP27 mRNAs, observed in human- and mouse-derived cell lines, is absent from cells with deleted, mutated or inactive p53, suggesting that regulation of SIP gene expression is dependent on p53. That hypothesis is consistent with the presence of a functional p53-response element within the promoter region of the mouse SIP gene and confirmed by the induction of SIP mRNA expression in mouse embryo fibroblasts upon activation of a p53-dependent pathway by transfection with rasV12 or rasV12/E1A. In conclusion, SIP being a proapoptotic gene induced through p53 activation could be a stress-induced gene with antitumour properties. 相似文献
186.
187.
188.
Expression profiling in pancreas during the acute phase of pancreatitis using cDNA microarrays 总被引:3,自引:0,他引:3
Dusetti NJ Tomasini R Azizi A Barthet M Vaccaro MI Fiedler F Dagorn JC Iovanna JL 《Biochemical and biophysical research communications》2000,277(3):660-667
Most attacks of acute pancreatitis are self-limiting, suggesting that the pancreatic cells adapt their phenotype to prevent progression of the disease. Such phenotypic change must involve a coordinated modification in the expression of numerous genes. To identify differentially expressed genes, high-density mouse cDNA microarrays were hybridized with cDNA probes from both healthy pancreas and pancreas affected by acute pancreatitis. From the 7981 mouse genes analyzed, 239 showed significant changes in their expression during the acute phase of pancreatitis. Among them, 107 genes were up-regulated whereas 132 were down-regulated. They include genes whose function was not previously related to pancreatitis, suggesting that they are involved in some way into the acute pancreatic response. Finally, 40% of differentially expressed genes corresponded to ESTs. Demonstration that a large quantity of unexpected or yet uncharacterized genes showed altered expression during acute pancreatitis underscores the interest of a genome-based investigation. Some of these genes are certainly involved in the cellular defense against pancreatitis and, as such, deserve being studied further. 相似文献
189.
Three series of 5-day submerged cultures with Pediococcus pentosaceus MITJ-10 and Lactobacillus acidophilus Hansen 1748 were carried out in starch-based media, and the effect of cultural factors on the changes of starch, diacetyl and amylase activity determined. In axenic cultures, Ped. pentosaceus MITJ-10 produced more diacetyl (63.27 mg l(-1)) by adding glucose, yeast extract and CaCO3 (P < 0.01), at 28 degrees C (P < 0.05); but more starch was consumed (18.4 g l(-1)) in the absence of glucose (P < 0.01). Lact. acidophilus Hansen 1748 consumed more starch (26.56 g l(-1)) at 28 degrees C, with CaCO3, glucose (P < 0.01) and yeast extract (P < 0.05); however, the amylolytic activity (10077U l(-1)) was favoured at 35 degrees C (P < 0.01). Little starch was consumed in mixed cultures due to the low pH; nevertheless, diacetyl content rose to 135.76 mg l(-1) at 32 degrees C (P < 0.01). Therefore, both studied strains might be useful to produce aromatic extensors from starchy substrates. These natural aromatic extensors are of interest to the food industry. 相似文献
190.
R Tomasini V Secq L Pouyet A K Thakur M Wilhelm J Nigri S Vasseur P Berthezene E Calvo G Melino T W Mak J L Iovanna 《Cell death and differentiation》2013,20(2):293-301
The multiple isoforms of p73, a member of the p53 family, share the ability to modulate p53 activities but also have unique properties, leading to a complex and poorly understood functional network. In vivo, p73 isoforms have been implicated in tumor suppression (TAp73−/− mice), DNA damage (ΔNp73−/− mice) and development (p73−/− mice). In this study, we investigated whether TAp73 contributes to innate immunity and septic shock. In response to a lethal lipopolysaccharide (LPS) challenge, TAp73−/− mice showed higher blood levels of proinflammatory cytokines and greater mortality than their wild-type littermates. In vitro, TAp73−/− macrophages exhibited elevated production of tumor necrosis factor alpha , interleukin-6 and macrophage inflammatory protein-2 as well as prolonged survival, decreased phagocytosis and increased major histocompatibility complex class II expression. Mice depleted of endogenous macrophages and reconstituted with TAp73−/− macrophages showed increased sensitivity to LPS challenge. These results suggest that macrophage polarization is altered in the absence of TAp73 such that maintenance of the M1 effector phenotype is prolonged at the expense of the M2 phenotype, thus impairing resolution of the inflammatory response. Our data indicate that TAp73 has a role in macrophage polarization and innate immunity, enhancing the action field of this important regulatory molecule. 相似文献