全文获取类型
收费全文 | 326篇 |
免费 | 17篇 |
出版年
2019年 | 1篇 |
2018年 | 4篇 |
2017年 | 2篇 |
2016年 | 6篇 |
2015年 | 14篇 |
2014年 | 15篇 |
2013年 | 23篇 |
2012年 | 13篇 |
2011年 | 14篇 |
2010年 | 24篇 |
2009年 | 24篇 |
2008年 | 13篇 |
2007年 | 12篇 |
2006年 | 11篇 |
2005年 | 13篇 |
2004年 | 11篇 |
2003年 | 3篇 |
2002年 | 4篇 |
2001年 | 6篇 |
2000年 | 4篇 |
1999年 | 3篇 |
1998年 | 9篇 |
1997年 | 10篇 |
1996年 | 4篇 |
1995年 | 6篇 |
1994年 | 3篇 |
1993年 | 7篇 |
1992年 | 3篇 |
1991年 | 5篇 |
1990年 | 2篇 |
1989年 | 5篇 |
1988年 | 11篇 |
1987年 | 5篇 |
1986年 | 2篇 |
1985年 | 4篇 |
1984年 | 5篇 |
1983年 | 5篇 |
1982年 | 16篇 |
1981年 | 3篇 |
1980年 | 1篇 |
1979年 | 2篇 |
1978年 | 2篇 |
1977年 | 5篇 |
1976年 | 3篇 |
1975年 | 3篇 |
1972年 | 1篇 |
1971年 | 1篇 |
排序方式: 共有343条查询结果,搜索用时 890 毫秒
241.
MCW Chan CY Cheung WH Chui SW Tsao JM Nicholls YO Chan RWY Chan HT Long LLM Poon Y Guan JSM Peiris 《Respiratory research》2005,6(1):135
Background
Fatal human respiratory disease associated with influenza A subtype H5N1 has been documented in Hong Kong, and more recently in Vietnam, Thailand and Cambodia. We previously demonstrated that patients with H5N1 disease had unusually high serum levels of IP-10 (interferon-gamma-inducible protein-10). Furthermore, when compared with human influenza virus subtype H1N1, the H5N1 viruses in 1997 (A/Hong Kong/483/97) (H5N1/97) were more potent inducers of pro-inflammatory cytokines (e.g. tumor necrosis factor-a) and chemokines (e.g. IP-10) from primary human macrophages in vitro, which suggests that cytokines dysregulation may play a role in pathogenesis of H5N1 disease. Since respiratory epithelial cells are the primary target cell for replication of influenza viruses, it is pertinent to investigate the cytokine induction profile of H5N1 viruses in these cells.Methods
We used quantitative RT-PCR and ELISA to compare the profile of cytokine and chemokine gene expression induced by H5N1 viruses A/HK/483/97 (H5N1/97), A/Vietnam/1194/04 and A/Vietnam/3046/04 (both H5N1/04) with that of human H1N1 virus in human primary alveolar and bronchial epithelial cells in vitro.Results
We demonstrated that in comparison to human H1N1 viruses, H5N1/97 and H5N1/04 viruses were more potent inducers of IP-10, interferon beta, RANTES (regulated on activation, normal T cell expressed and secreted) and interleukin 6 (IL-6) in primary human alveolar and bronchial epithelial cells in vitro. Recent H5N1 viruses from Vietnam (H5N1/04) appeared to be even more potent at inducing IP-10 than H5N1/97 virus.Conclusion
The H5N1/97 and H5N1/04 subtype influenza A viruses are more potent inducers of proinflammatory cytokines and chemokines in primary human respiratory epithelial cells than subtype H1N1 virus. We suggest that this hyper-induction of cytokines may be relevant to the pathogenesis of human H5N1 disease. 相似文献242.
243.
244.
Bernadette Pignol Sylvie Hnane Jean-Michel Mencia-Huerta Marek Rola-Pleszczynski Pierre Braquet 《Prostaglandins & other lipid mediators》1987,33(6)
PAF-acether, at doses ranging from 1pM to 0.1μM did not induce a significative release and/or synthesis of IL1 from monocytes. In contrast, depending upon the dose of the mediator, adverse effects on the lipopolysaccharide (LPS)-induced IL1 release and synthesis were observed. PAF-acether at 1pM increased IL1 release by 120 ± 39% and synthesis by 87 ± 27% whereas at 0.1μM a decrease of IL1 release of 52 ± 9% and synthesis of 46 ± 6% were observed. BN 52021, a specific PAF-acether receptor antagonist, reversed by more than 70% the increase or inhibition of LPS-induced IL1 release and synthesis induced by 1pM and 0.1μM of the autacoid, respectively. No direct effect of BN 52021 on IL1 release and synthesis from adherent monocytes was noted. These results indicate that PAF-acether modulates monocyte functions, possibly
specific binding sites. 相似文献
245.
246.
Evolution of the secondary structures and compensatory mutations of the ribosomal RNAs of Drosophila melanogaster 总被引:10,自引:0,他引:10
This paper examines the effects of DNA sequence evolution on RNA secondary
structures and compensatory mutations. Models of the secondary structures
of Drosophila melanogaster 18S ribosomal RNA (rRNA) and of the complex
between 2S, 5.8S, and 28S rRNAs have been drawn on the basis of comparative
and energetic criteria. The overall AU richness of the D. melanogaster
rRNAs allows the resolution of some ambiguities in the structures of both
large rRNAs. Comparison of the sequence of expansion segment V2 in D.
melanogaster 18S rRNA with the same region in three other Drosophila
species and the tsetse fly (Glossina morsitans morsitans) allows us to
distinguish between two models for the secondary structure of this region.
The secondary structures of the expansion segments of D. melanogaster 28S
rRNA conform to a general pattern for all eukaryotes, despite having highly
divergent sequences between D. melanogaster and vertebrates. The 70 novel
compensatory mutations identified in the 28S rRNA show a strong (70%) bias
toward A-U base pairs, suggesting that a process of biased mutation and/or
biased fixation of A and T point mutations or AT-rich slippage-generated
motifs has occurred during the evolution of D. melanogaster rDNA. This
process has not occurred throughout the D. melanogaster genome. The
processes by which compensatory pairs of mutations are generated and spread
are discussed, and a model is suggested by which a second mutation is more
likely to occur in a unit with a first mutation as such a unit begins to
spread through the family and concomitantly through the population.
Alternatively, mechanisms of proofreading in stem-loop structures at the
DNA level, or between RNA and DNA, might be involved. The apparent
tolerance of noncompensatory mutations in some stems which are otherwise
strongly supported by comparative criteria within D. melanogaster 28S rRNA
must be borne in mind when compensatory mutations are used as a criterion
in secondary-structure modeling. Noncompensatory mutation may extend to the
production of unstable structures where a stem is stabilized by RNA-
protein or additional RNA-RNA interactions in the mature ribosome. Of
motifs suggested to be involved in rRNA processing, one (CGAAAG) is
strongly overrepresented in the 28S rRNA sequence. The data are discussed
both in the context of the forces involved with the evolution of multigene
families and in the context of molecular coevolution in the rDNA family in
particular.
相似文献
247.
248.
249.
Heterologous expression of an engineered truncated form of human Lewis fucosyltransferase (Fuc-TIII) by the methylotrophic yeast Pichia pastoris 总被引:1,自引:0,他引:1
Gallet PF; Vaujour H; Petit JM; Maftah A; Oulmouden A; Oriol R; Le Narvor C; Guilloton M; Julien R 《Glycobiology》1998,8(9):919-925
A stable GS115 Pichia pastoris recombinant strain was constructed to
secrete a truncated form of the human alpha(1,3/4) fucosyltransferase
(amino acids 45-361). Enzyme production resulted from a secretory pathway
based on the pre-pro- alpha mating factor signal sequence of the yeast
Saccharomyces cerevisiae . Following its transit through the Golgi
apparatus, the enzyme accumulated in the periplasmic space before its
release in the culture broth (about 30 mg/l). Cell-enclosed enzyme (
approximately 0.16%) proved to be fairly stable for many freezing and
thawing cycles and could be used several times as an immobilized catalyst.
Soluble enzyme (>99.8%) representing the main protein of the culture
broth (10%) has been characterized by Western-blotting, substrate
specificities and kinetic parameters. The two forms (cell- enclosed and
soluble) of recombinant enzyme may be used for in vitro synthesis of
Lewisadeterminants.
相似文献
250.
Worldwide patterns of mitochondrial DNA differentiation in the harbor seal (Phoca vitulina) 总被引:3,自引:0,他引:3
Stanley HF; Casey S; Carnahan JM; Goodman S; Harwood J; Wayne RK 《Molecular biology and evolution》1996,13(2):368-382
The harbor seal (Phoca vitulina) has one of the broadest geographic
distributions of any pinniped, stretching from the east Baltic, west across
the Atlantic and Pacific Oceans to southern Japan. Although individuals may
travel several hundred kilometers on annual feeding migrations, harbor
seals are generally believed to be philopatric, returning to the same areas
each year to breed. Consequently, seals from different areas are likely to
be genetically differentiated, with levels of genetic divergence increasing
with distance. Differentiation may also be caused by long-standing
topographic barriers such as the polar sea ice. We analyzed samples of 227
harbor seals from 24 localities and defined 34 genotypes based on 435 bp of
control region sequence. Phylogenetic analysis and analysis of molecular
variance showed that populations in the Atlantic and Pacific Oceans and
east and west coast populations of these oceans are significantly
differentiated. Within these four regions, populations that are
geographically farthest apart generally are the most differentiated and
often do not share genotypes or differ in genotype frequency. The average
corrected sequence divergence between populations in the Atlantic and
Pacific Oceans is 3.28% +/- 0.38% and those among populations within each
of these oceans are 0.75% +/- 0.69% and 1.19% +/- 0.65%, respectively. Our
results suggest that harbor seals are regionally philopatric, on the scale
of several hundred kilometers. However, genetic discontinuities may exist,
even between neighboring populations such as those on the Scottish and east
English coasts or the east and west Baltic. The mitochondrial data are
consistent with an ancient isolation of populations in both oceans, due to
the development of polar sea ice. In the Atlantic and Pacific, populations
appear to have been colonized from west to east with the European
populations showing the most recent common ancestry. We suggest the recent
ancestry of European seal populations may reflect recolonization from Ice
Age refugia after the last glaciation.
相似文献