全文获取类型
收费全文 | 183篇 |
免费 | 20篇 |
专业分类
203篇 |
出版年
2019年 | 3篇 |
2017年 | 2篇 |
2016年 | 5篇 |
2015年 | 12篇 |
2014年 | 12篇 |
2013年 | 6篇 |
2012年 | 8篇 |
2011年 | 16篇 |
2010年 | 2篇 |
2009年 | 9篇 |
2008年 | 10篇 |
2006年 | 9篇 |
2005年 | 4篇 |
2004年 | 4篇 |
2003年 | 5篇 |
2002年 | 2篇 |
2001年 | 4篇 |
2000年 | 2篇 |
1999年 | 3篇 |
1998年 | 10篇 |
1997年 | 3篇 |
1996年 | 2篇 |
1993年 | 2篇 |
1992年 | 6篇 |
1989年 | 4篇 |
1986年 | 2篇 |
1984年 | 2篇 |
1983年 | 4篇 |
1982年 | 2篇 |
1979年 | 4篇 |
1978年 | 4篇 |
1977年 | 3篇 |
1975年 | 4篇 |
1974年 | 2篇 |
1973年 | 1篇 |
1972年 | 1篇 |
1971年 | 2篇 |
1970年 | 1篇 |
1968年 | 1篇 |
1954年 | 1篇 |
1942年 | 1篇 |
1936年 | 1篇 |
1932年 | 1篇 |
1923年 | 1篇 |
1921年 | 1篇 |
1914年 | 2篇 |
1913年 | 1篇 |
1912年 | 3篇 |
1901年 | 1篇 |
1875年 | 1篇 |
排序方式: 共有203条查询结果,搜索用时 15 毫秒
1.
Assignment of genes encoding a unique cytokine (IL12) composed of two unrelated subunits to chromosomes 3 and 5. 总被引:14,自引:0,他引:14
D Sieburth E W Jabs J A Warrington X Li J Lasota S LaForgia K Kelleher K Huebner J J Wasmuth S F Wolf 《Genomics》1992,14(1):59-62
IL12 (formerly NKSF or CLMF) is a unique cytokine composed of two unrelated disulfide-linked subunits. The larger 40-kDa subunit (p40) is a member of the cytokine receptor family, and the smaller 35-kDa subunit (p35) is related to IL6 and GCSF. The chromosomal localization of these two subunits was determined by PCR analysis of DNA from rodent-human hybrids. More refined mapping was obtained by PCR analysis of hybrids containing translocation chromosomes and for p40, by analysis of radiation hybrids. The subunits map to different chromosomes: p40 (IL12B) to 5q31-q33 and p35 (IL12A) to 3p12-3q13.2. 相似文献
2.
Gold salts and phenylbutazone selectively inhibit the synthesis of PGF2α and PGE2 respectively. Lowered production of one prostaglandin species is accompanied by an increased production of the other. Selective inhibition by these drugs was observed in the presence of adrenaline, reduced glutathione and copper sulphate under conditions when most anti-inflammatory compounds inhibited PGE2 and PGF2α syntheses equally. It is postulated that selective inhibitors may have a different mode of action
and beneficial effects may be related to the endogenous ratio of PGE to PGF required for normal function. 相似文献
3.
Multicellular eukaryotes contain a macromolecular assembly of nine aminoacyl-tRNA synthetase activities and three auxiliary proteins. One of these, p43, is the precursor of endothelial monocyte-activating polypeptide II (EMAP II), an inflammatory cytokine involved in apoptotic processes. As a step toward understanding this paradoxical association, the EMAP II portion of p43 has been localized within the rabbit reticulocyte multisynthetase complex. Immunoblot analysis demonstrates strong reaction of anti-EMAP II antiserum with p43, as well as cross-reactivity with isoleucyl-tRNA synthetase. Electron microscopic images of immunocomplexes show two antibody binding sites. The primary site is near the midpoint of the multisynthetase complex at the intersection of the arms with the base. This site near the lower edge of the central cleft is assigned to the C-terminal cytokine portion of p43. The secondary site of antibody binding is in the base of the particle and maps the location of isoleucyl-tRNA synthetase. These data allow refinement of the three-domain model of polypeptide distribution within the multisynthetase complex. Moreover, the central location of p43/EMAP II suggests a role for this polypeptide in optimizing normal function and in rapid disruption of essential cellular machinery when apoptosis is signaled. 相似文献
4.
David Mesher Elaine Stanford Joanne White Jamie Findlow Rosalind Warrington Sukamal Das Richard Pebody Ray Borrow Kate Soldan 《PloS one》2016,11(3)
Background
Reported human papillomavirus (HPV) vaccination coverage in England is high, particularly in girls offered routine immunisation at age 12 years. Serological surveillance can be used to validate reported coverage and explore variations within it and changes in serological markers over time.Methods
Residual serum specimens collected from females aged 15–19 years in 2010–2011 were tested for anti-HPV16 and HPV18 IgG by ELISA. Based on these results, females were classified as follows: seronegative, probable natural infection, probable vaccine-induced seropositivity, or possible natural infection/possible vaccine-induced seropositivity. The proportion of females with vaccine-induced seropositivity was compared to the reported vaccination coverage.Results
Of 2146 specimens tested, 1380 (64%) were seropositive for both types HPV16 and HPV18 and 159 (7.4%) positive for only one HPV type. The IgG concentrations were far higher for those positive for both HPV types than those positive for only one HPV type. 1320 (62%) females were considered to have probable vaccine-induced seropositivity. Among vaccine-induced seropositives, antibody concentrations declined with increasing age at vaccination and increasing time since vaccination.Conclusions
The proportion of females with vaccine-induced seropositivity was closest to the reported 3-dose coverage in those offered the vaccination at younger ages, with a greater discrepancy in the older females. This suggests either some under-reporting of immunisations of older females and/or that partial vaccination (i.e. one- or two-doses) has provided high antibody responses in 13–17 year olds. 相似文献5.
Identification of amino acid residues in the capsid proteins of adeno-associated virus type 2 that contribute to heparan sulfate proteoglycan binding 总被引:9,自引:0,他引:9 下载免费PDF全文
Opie SR Warrington KH Agbandje-McKenna M Zolotukhin S Muzyczka N 《Journal of virology》2003,77(12):6995-7006
The adeno-associated virus type 2 (AAV2) uses heparan sulfate proteoglycan (HSPG) as its primary cellular receptor. In order to identify amino acids within the capsid of AAV2 that contribute to HSPG association, we used biochemical information about heparin and heparin sulfate, AAV serotype protein sequence alignments, and data from previous capsid studies to select residues for mutagenesis. Charged-to-alanine substitution mutagenesis was performed on individual residues and combinations of basic residues for the production and purification of recombinant viruses that contained a green fluorescent protein (GFP) reporter gene cassette. Intact capsids were assayed for their ability to bind to heparin-agarose in vitro, and virions that packaged DNA were assayed for their ability to transduce normally permissive cell lines. We found that mutation of arginine residues at position 585 or 588 eliminated binding to heparin-agarose. Mutation of residues R484, R487, and K532 showed partial binding to heparin-agarose. We observed a general correlation between heparin-agarose binding and infectivity as measured by GFP transduction; however, a subset of mutants that partially bound heparin-agarose (R484A and K532A) were completely noninfectious, suggesting that they had additional blocks to infectivity that were unrelated to heparin binding. Conservative mutation of positions R585 and R588 to lysine slightly reduced heparin-agarose binding and had comparable effects on infectivity. Substitution of AAV2 residues 585 through 590 into a location predicted to be structurally equivalent in AAV5 generated a hybrid virus that bound to heparin-agarose efficiently and was able to package DNA but was noninfectious. Taken together, our results suggest that residues R585 and R588 are primarily responsible for heparin sulfate binding and that mutation of these residues has little effect on other aspects of the viral life cycle. Interactive computer graphics examination of the AAV2 VP3 atomic coordinates revealed that residues which contribute to heparin binding formed a cluster of five basic amino acids that presented toward the icosahedral threefold axis from the surrounding spike protrusion. Three other kinds of mutants were identified. Mutants R459A, H509A, and H526A/K527A bound heparin at levels comparable to that of wild-type virus but were defective for transduction. Another mutant, H358A, was defective for capsid assembly. Finally, an R459A mutant produced significantly lower levels of full capsids, suggesting a packaging defect. 相似文献
6.
Pasquier CM; Promponas VI; Varvayannis NJ; Hamodrakas SJ 《Bioinformatics (Oxford, England)》1998,14(8):749-750
Summary : FT is a tool written in C++, which implements the Fourier
analysis method to locate periodicities in aminoacid or DNA sequences. It
is provided for free public use on a WWW server with a Java interface.
Availability : The server address is http://o2.db. uoa.gr/FT Contact :
shamodr@atlas.uoa.gr
相似文献
7.
JF Yuan SJ Zhang O Jafer RA Furlong OE Chausiaux CA Sargent GH Zhang NA Affara 《BMC microbiology》2009,9(1):246
Background
Pseudorabies virus (PRV) is an alphaherpesviruses whose native host is pig. PRV infection mainly causes signs of central nervous system disorder in young pigs, and respiratory system diseases in the adult. 相似文献8.
In a variety of tumour systems, individuals carrying progressively growing neoplasms have lymphoid cells with a specific cytotoxic effect on cultured tumour cells from the same individual1–4. Since the sera of tumour-bearing individuals have been shown to prevent tumour cell destruction by immune lymphocytes in vitro2,5–8 and since this serum blocking activity appears early in primary and transplant tumour development5,7, it has been suggested that the appearance of this serum blocking activity might be responsible for the progressive growth of tumours in individuals having cytotoxic lymphocytes. Counteraction of this blocking activity would thus be of primary importance in facilitating the function of an already existing or bolstered cell-mediated immunity. The serum blocking activity might be inhibited in various ways, by preventing the formation of blocking antibody or by interfering with its action (“unblocking”), as demonstrated in Moloney sarcoma regressor sera9. This type of serum also has a therapeutic effect on Moloney sarcomas in vivo10,11, which has been tentatively attributed to its unblocking activity8,9 or, possibly, to a complement-dependent cytotoxicity10. Tumour growth in the Moloney sarcoma system, however, might be due in part to continuous recruitment of neoplastic cells by virus-induced transformation and so the therapeutic effect could be due to a virus-neutralizing serum activity9,10. 相似文献
9.
10.