全文获取类型
收费全文 | 309篇 |
免费 | 24篇 |
专业分类
333篇 |
出版年
2023年 | 2篇 |
2022年 | 1篇 |
2021年 | 4篇 |
2020年 | 2篇 |
2019年 | 2篇 |
2018年 | 5篇 |
2017年 | 6篇 |
2016年 | 3篇 |
2015年 | 10篇 |
2014年 | 8篇 |
2013年 | 13篇 |
2012年 | 10篇 |
2011年 | 17篇 |
2010年 | 12篇 |
2009年 | 14篇 |
2008年 | 16篇 |
2007年 | 11篇 |
2006年 | 16篇 |
2005年 | 13篇 |
2004年 | 27篇 |
2003年 | 15篇 |
2002年 | 14篇 |
2001年 | 10篇 |
2000年 | 16篇 |
1999年 | 13篇 |
1998年 | 6篇 |
1997年 | 6篇 |
1996年 | 4篇 |
1995年 | 5篇 |
1994年 | 5篇 |
1993年 | 2篇 |
1992年 | 1篇 |
1991年 | 2篇 |
1990年 | 1篇 |
1989年 | 3篇 |
1988年 | 7篇 |
1987年 | 7篇 |
1986年 | 5篇 |
1985年 | 1篇 |
1983年 | 1篇 |
1980年 | 1篇 |
1979年 | 1篇 |
1978年 | 4篇 |
1977年 | 3篇 |
1976年 | 3篇 |
1975年 | 1篇 |
1974年 | 1篇 |
1971年 | 1篇 |
1970年 | 1篇 |
1967年 | 1篇 |
排序方式: 共有333条查询结果,搜索用时 15 毫秒
1.
Large fragments of nef-protein and gp110 envelope glycoprotein from HIV-1. Synthesis, CD analysis and immunoreactivity 总被引:1,自引:0,他引:1
J M Sabatier G Fontan E Loret K Mabrouk H Rochat J C Gluckman L Montagnier C Granier E Bahraoui J Van Rietschoten 《International journal of peptide and protein research》1990,35(1):63-72
Chemical synthesis of large peptide fragments (from 18 to 66 amino acid residues long) of the gp110 envelope glycoprotein and of nef-protein from HIV-1 was achieved by the solid phase method. Stepwise assembling of the peptide chains was carried out automatically on 4-(oxymethyl)-phenylacetamidomethyl resin using the N-alpha-butyloxycarbonyl amino acids with benzyl-based side chain protecting groups. Two elongation protocols were used depending on the peptide chain length: a standard cycle, mainly characterized by a single coupling step (Boc-amino acid symmetrical anhydride in dimethylformamide), and an optimized one for large peptides, based on a double coupling strategy (Boc-amino acid symmetrical anhydride first in dimethylformamide, then in dichloromethane). Final cleavage of the peptide from the solid support was carried out by anhydrous hydrogen fluoride and crude peptides were purified by C18 reverse phase medium pressure liquid chromatography after molecular filtration. Characterization of the purified peptides was done by analytical HPLC, amino acid content determination, and circular dichroism analysis both in polar (H2O) and in non-polar (TFE) environments. Immunoreactivity of anti-nef positive sera from HIV-1 infected patients by ELISA with the synthetic peptides was investigated. The results showed four major antigenic regions of nef-protein and mainly the immunodominance of the N- and C-termini of the molecule. Several of these peptides should prove to be useful for both diagnosis and vaccination purposes. 相似文献
2.
Telomeres gradually shorten as human somatic cells divide and a correlation has been observed between the average telomere length and cell senescence. It has been proposed that the genes responsible for cell senescence are located near the telomere and are activated when telomere length reaches a critical point. This is consistent with evidence from Saccharomyces cerevisiae, in which genes are regulated differently depending on their distance from the telomere. We investigated the possibility that differential gene expression is conferred by telomere length in human cells. A plasmid containing the neomycin phosphotransferase (neo) gene was transfected into the SV40-transformed human fibroblast cell line LM217. In one transfectant the plasmid was integrated at the telomere of chromosome 13. Subclones of this cell line that had various lengths of telomeric repeat sequences on the end of this chromosome were isolated. No effect on neo gene expression was found when the length of the telomere varied between 25 and 0.5 kb, as demonstrated by colony forming ability, growth rates and RNA blot analysis. These results therefore suggest that putative chromatin structural differences conferred by telomere length do not affect the expression of genes located near telomeres. 相似文献
3.
The integration of transfected plasmid DNA at the telomere of chromosome 13 in an immortalized simian virus 40-transformed human cell line provided the first opportunity to study polymorphism in the number of telomeric repeat sequences on the end of a single chromosome. Three subclones of this cell line were selected for analysis: one with a long telomere on chromosome 13, one with a short telomere, and one with such extreme polymorphism that no distinct band was discernible. Further subcloning demonstrated that telomere polymorphism resulted from both gradual changes and rapid changes that sometimes involved many kilobases. The gradual changes were due to the shortening of telomeres at a rate similar to that reported for telomeres of somatic cells without telomerase, eventually resulting in the loss of nearly all of the telomere. However, telomeres were not generally lost completely, as shown by the absence of polymorphism in the subtelomeric plasmid sequences. Instead, telomeres that were less than a few hundred base pairs in length showed a rapid, highly heterogeneous increase in size. Rapid changes in telomere length also occurred on longer telomeres. The frequency of this type of change in telomere length varied among the subclones and correlated with chromosome fusion. Therefore, the rapid changes in telomere length appeared occasionally to result in the complete loss of telomeric repeat sequences. Rapid changes in telomere length have been associated with telomere loss and chromosome instability in yeast and could be responsible for the high rate of chromosome fusion observed in many human tumor cell lines. 相似文献
4.
Sarrah M'Barek Ziad Fajloun Sandrine Cestle Christiane Devaux Pascal Mansuelle Amor Mosbah Besma Jouirou Massimo Mantegazza Jurphaas van Rietschoten Mohamed El Ayeb Herv Rochat Jean‐Marc Sabatier Francois Sampieri 《Journal of peptide science》2004,10(11):666-677
Aah I is a 63-residue alpha-toxin isolated from the venom of the Buthidae scorpion Androctonus australis hector, which is considered to be the most dangerous species. We report here the first chemical synthesis of Aah I by the solid-phase method, using a Fmoc strategy. The synthetic toxin I (sAah I) was renatured in DMSO-Tris buffer, purified and subjected to thorough analysis and comparison with the natural toxin. The sAah I showed physico-chemical (CD spectrum, molecular mass, HPLC elution), biochemical (amino-acid composition, sequence), immunochemical and pharmacological properties similar to those of the natural toxin. The synthetic toxin was recognized by a conformation-dependent monoclonal anti-Aah I antibody, with an IC50 value close to that for the natural toxin. Following intracerebroventricular injection, the synthetic and the natural toxins were similarly lethal to mice. In voltage-clamp experiments, Na(v) 1.2 sodium channel inactivation was inhibited by the application of sAah I or of the natural toxin in a similar way. This work describes a simple protocol for the chemical synthesis of a scorpion alpha-toxin, making it possible to produce structural analogues in time. 相似文献
5.
R-banded karyotypes were established on fibroblasts from fibrotic tissues derived from experimental fibrosis induced in pigs, either surgically or by 64 Gy of gamma-rays from iridium-192. No chromosome aberrations were observed in the surgical fibrosis. In radiation-induced fibrosis, the high frequency of abnormal karyotypes and the frequent complexity of the chromosomal rearrangements suggest that the fibroblasts originated either from the 64-Gy area, or from the penumbra, but certainly not from non-irradiated areas. At early passages in vitro, almost all karyotypes were different, demonstrating a multiclonal origin of fibrotic tissue. At late passages (above 24), the situation was quite different, with the persistence of one or two clones only, demonstrating a strong selective pressure occurring in vitro. 相似文献
6.
A specific immunological probe for the major myelin proteolipid. Confirmation of a deletion in DM-20 总被引:6,自引:0,他引:6
E Trifilieff B Luu J L Nussbaum G Roussel A Espinosa de los Monteros J M Sabatier J Van Rietschoten 《FEBS letters》1986,198(2):235-239
Major myelin proteolipid (MMPL, also called PLP) and DM-20 are the two major intrinsic membrane proteins of CNS myelin. A specific immunological probe was obtained for MMPL by raising antibodies against the synthetic tridecapeptide 117-129 of MMPL. Antibodies against this peptide reacted with the MMPL but did not cross react with DM-20, while both proteolipids had been shown previously to be recognized by antibodies directed against the C-terminal hexapeptide of MMPL. This is in accordance with previous findings showing that DM-20 differs only from MMPL by a deletion of residues 100-140 (+/- few units). Furthermore, this site-specific immunological probe also recognizes MMPL in its native form in oligodendrocytes in primary glial cell cultures. 相似文献
7.
MARIA JOSÉ ASINS IRENE VILLALTA MOHAMED M. ALY RAQUEL OLÍAS PAZ ÁLVAREZ DE MORALES RAÚL HUERTAS JUN LI NOELIA JAIME‐PÉREZ ROSARIO HARO VERÓNICA RAGA EMILIO A. CARBONELL ANDRÉS BELVER 《Plant, cell & environment》2013,36(6):1171-1191
The location of major quantitative trait loci (QTL) contributing to stem and leaf [Na+] and [K+] was previously reported in chromosome 7 using two connected populations of recombinant inbred lines (RILs) of tomato. HKT1;1 and HKT1;2, two tomato Na+‐selective class I‐HKT transporters, were found to be closely linked, where the maximum logarithm of odds (LOD) score for these QTLs located. When a chromosome 7 linkage map based on 278 single‐nucleotide polymorphisms (SNPs) was used, the maximum LOD score position was only 35 kb from HKT1;1 and HKT1;2. Their expression patterns and phenotypic effects were further investigated in two near‐isogenic lines (NILs): 157‐14 (double homozygote for the cheesmaniae alleles) and 157‐17 (double homozygote for the lycopersicum alleles). The expression pattern for the HKT1;1 and HKT1;2 alleles was complex, possibly because of differences in their promoter sequences. High salinity had very little effect on root dry and fresh weight and consequently on the plant dry weight of NIL 157‐14 in comparison with 157‐17. A significant difference between NILs was also found for [K+] and the [Na+]/[K+] ratio in leaf and stem but not for [Na+] arising a disagreement with the corresponding RIL population. Their association with leaf [Na+] and salt tolerance in tomato is also discussed. 相似文献
8.
Background
Existing cut-offs for fasting plasma glucose (FPG) and post-load glucose (2hPG) criteria are not equivalent in the diagnosis of diabetes and glucose intolerance. Adjusting cut-offs of single measurements have not helped so we undertook this project to see if they could be complementary. 相似文献9.
JOSÉ ANTONIO FERNÁNDEZ PRIETO CARLOS AGUIAR EDUARDO DIAS MARIA ISABEL GUTIÉRREZ VILLARÍAS 《Botanical journal of the Linnean Society. Linnean Society of London》2008,157(3):493-499
The majority of authors consider Festuca jubata Lowe as an endemic species common to Madeira and the Azores. Saint-Yves proposed that F. jubata was an Azorean endemic and described a geovicarious taxon in Madeira: F. filiformis C. Sm. ex Link in Buch ssp. mandonii St.-Yves. We undertook a complete bibliographical revision of the taxonomy, nomenclature, and chorology of F. jubata s.l. , and contrasted it with morphological and anatomical studies performed on samples from the Azores and Madeira. Azorean plants usually identified as F. jubata had a character combination distinct from that of those with a Madeiran provenance. Saint-Yves' proposal of two independent taxa was correct, but he erroneously considered F. jubata as an Azorean endemic because the name F. jubata was based on Madeiran plants. Consequently, F. jubata auct. pl. from the Azores belongs to a new species. © 2008 The Linnean Society of London, Botanical Journal of the Linnean Society , 2008, 157 , 493–499. 相似文献
10.