全文获取类型
收费全文 | 241篇 |
免费 | 20篇 |
出版年
2023年 | 1篇 |
2022年 | 2篇 |
2021年 | 4篇 |
2020年 | 1篇 |
2019年 | 1篇 |
2018年 | 1篇 |
2017年 | 5篇 |
2016年 | 3篇 |
2015年 | 11篇 |
2014年 | 18篇 |
2013年 | 18篇 |
2012年 | 17篇 |
2011年 | 9篇 |
2010年 | 9篇 |
2009年 | 13篇 |
2008年 | 12篇 |
2007年 | 10篇 |
2006年 | 12篇 |
2005年 | 12篇 |
2004年 | 11篇 |
2003年 | 5篇 |
2002年 | 4篇 |
2001年 | 13篇 |
2000年 | 10篇 |
1999年 | 4篇 |
1998年 | 11篇 |
1997年 | 4篇 |
1996年 | 3篇 |
1995年 | 3篇 |
1994年 | 3篇 |
1993年 | 2篇 |
1990年 | 1篇 |
1989年 | 1篇 |
1988年 | 3篇 |
1987年 | 3篇 |
1985年 | 1篇 |
1984年 | 2篇 |
1983年 | 3篇 |
1982年 | 1篇 |
1981年 | 1篇 |
1979年 | 1篇 |
1977年 | 2篇 |
1976年 | 2篇 |
1975年 | 1篇 |
1974年 | 1篇 |
1972年 | 1篇 |
1971年 | 2篇 |
1969年 | 1篇 |
1967年 | 1篇 |
1934年 | 1篇 |
排序方式: 共有261条查询结果,搜索用时 15 毫秒
101.
Bellis M; Jubier-Maurin V; Dod B; Vanlerberghe F; Laurent AM; Senglat C; Bonhomme F; Roizes G 《Molecular biology and evolution》1987,4(4):351-363
The presence of the L1 sequences, L1Md4 next to the pseudogene beta h3 and
I12 found in the twelfth intron of the albumin gene, in certain strains of
laboratory mice but not of others has led to the suggestion that these
sequences were recent insertions into the Mus mus domesticus genome. To be
sure that they are really recent insertions and not relics of an ancestral
chromosome, we investigated the presence or absence of these sequences in
populations of wild mice belonging to the semispecies M. m. domesticus and
M. m. musculus as well as in other species of the genus Mus and in related
murids. The sequence I12 in the albumin gene was found in 34% of the
chromosomes of the wild mice belonging to M. m. domesticus and to a lesser
extent (6%) in M. m. musculus. Of 114 M. m. domesticus chromosomes, L1Md4
was found in only nine, seven of which came from the same locality. Its
presence was associated with the haplotype Hbbp, which is relatively rare
in European populations of M. musculus. Since there was no evidence for the
presence of these two L1 sequences in more distantly related species, we
conclude that they are recent insertions in the M. musculus genome.
相似文献
102.
B Chevassus JM Blanc P Bergot L Casenave AM Escaffre F Hérioux N Kaushik R Lanneberre 《遗传、选种与进化》1979,11(1):79-92
103.
Bassi AM Romano P Mangini S Colombo M Canepa C Nanni G Casu A 《Journal of biomedical science》2005,12(3):457-466
Summary We analysed the action, in rats in vivo, of the protein isoprenylation inhibitor perillyl alcohol (POH) and that of vitamin A, alone or in association, on m-RNA and protein expression of farnesyltransferases (FTases α and β subunits) and their protein substrates RhoA and RhoB, in isolated hepatocytes. Combined administration of POH and vitamin A induced a sharp decrease in FTase α protein after 96 h, suggesting an involvement not only of farnesyltransferases but also of geranylgeranyltransferases, which share the FTase α protein. FTase β protein did not decrease. POH plus vitamin A, in contrast with POH or vitamin A alone, induced a decrease in RhoB protein, probably because of different cleavages. No modification was observed in RhoA protein. Vitamin A alone increased RhoB m-RNA and protein expression. As one of the functions of RhoB is cell polarisation, these data support our previous hypothesis of a polarised transport of vitamin A from hepatocytes to hepatic stellate cells. As the behaviours of m-RNAs and proteins in this study were often different, cytoplasmic metabolic pathways must be considered for the parameters studied. The behaviour of Rho B, which is thought to have an antioncogene function, is discussed in view of its isoprenylated forms in the membranes. These preliminary findings stress the need, when studying the association of two isoprenoids in cancer therapy, to consider normal as well as tumour-bearing animals. 相似文献
104.
Luo J Zhang L Stenn K Prouty S Parimoo S 《Biochemical and biophysical research communications》2005,327(1):64-69
Plucked (pk) is an autosomal recessive mouse mutation with a hair phenotype that arose spontaneously in the DBA/2J strain. Histological studies indicate that adult pk mutant mice lose truncal hair because of the scarring of follicles due to an apparent obstruction of the outward movement of the hair shaft within the follicular canal. We mapped the pk mutant phenotype to a 1.1cM region of chromosome 18 (between 6.6 and 7.7 cM from the centromere) using 370 backcross progeny. Within this region, among others, are genes for desmosome cadherins. Desmosome cadherins are interesting candidates because of their critical roles for cell-cell adhesion in epidermal function. Northern Blot analysis of wild-type and pk mutant mice indicates that expression of both desmoglein 1 (Dsg1) and desmoglein 3 (Dsg3) is up-regulated in the skin of mutant pk mice. 相似文献
105.
Dyatkin AB Gong Y Miskowski TA Kimball ES Prouty SM Fisher MC Santulli RJ Schneider CR Wallace NH Hornby PJ Diamond C Kinney WA Maryanoff BE Damiano BP He W 《Bioorganic & medicinal chemistry》2005,13(24):6693-6702
A series of N-carboxy, N-alkyl, and N-carboxamido azabicyclo[2.2.2]octane carboxamides were prepared and assayed for inhibition of alpha4beta1-VCAM-1 and alpha4beta7-MAdCAM-1 interactions. Potency and alpha4beta1/alpha4beta7 selectivity were sensitive to the substituent R1-R3 in the structures 6, 7, and 8. Several compounds demonstrated low nanomolar balanced alpha4beta1/alpha4beta7 in vitro activity. Two compounds were selected for in vivo leukocytosis studies and demonstrated increases in circulating lymphocytes up to 250% over control. 相似文献
106.
Lotus corniculatus nodulation specificity is changed by the presence of a soybean lectin gene 总被引:5,自引:0,他引:5 下载免费PDF全文
Plant lectins have been implicated as playing an important role in mediating recognition and specificity in the Rhizobium-legume nitrogen-fixing symbiosis. To test this hypothesis, we introduced the soybean lectin gene Le1 either behind its own promoter or behind the cauliflower mosaic virus 35S promoter into Lotus corniculatus, which is nodulated by R. loti. We found that nodulelike outgrowths developed on transgenic L. corniculatus plant roots in response to Bradyrhizobium japonicum, which nodulates soybean and not Lotus spp. Soybean lectin was properly targeted to L. corniculatus root hairs, and although infection threads formed, they aborted in epidermal or hypodermal cells. Mutation of the lectin sugar binding site abolished infection thread formation and nodulation. Incubation of bradyrhizobia in the nodulation (nod) gene-inducing flavonoid genistein increased the number of nodulelike outgrowths on transgenic L. corniculatus roots. Studies of bacterial mutants, however, suggest that a component of the exopolysaccharide surface of B. japonicum, rather than Nod factor, is required for extension of host range to the transgenic L. corniculatus plants. 相似文献
107.
Fitness effects of amino acid replacements in the beta-galactosidase of Escherichia coli 总被引:7,自引:1,他引:6
Two genetic procedures were used to obtain amino acid replacements in the
lacZ-encoded beta-galactosidase in Escherichia coli. Amino acid
replacements could be obtained without regard to their effects on lactase
activity by selecting spontaneous mutations that relieved the strong
polarity of six nonsense mutations. When streaked on MacConkey- lactose
indicator plates, approximately 75% of these mutants gave strong red
lactose-fermenting colonies, and 25% gave white nonfermenting colonies.
Mutants from 11 other nonsense codons were isolated directly using
MacConkey-lactose indicator plates, on which positive color indication
requires only 0.5% of the wildtype lactase activity. Among the total of 17
codons, 25 variant beta-galactosidases were identified using
electrophoresis and thermal denaturation studies. The fitness effects of
these variant beta-galactosidases were determined using competition
experiments conducted with lactose as the sole nutrient limiting the growth
rate in chemostat cultures. Three of the replacements were deleterious, one
was selectively advantageous, and the selective effects of the remaining 21
were undetectable under conditions in which the smallest detectable
selection coefficient was approximately 0.4%/generation.
相似文献
108.
RC Pritchett AM Al-Nawaiseh KK Pritchett V Nethery PA Bishop JM Green 《Biology of sport / Institute of Sport》2015,32(3):249-254
Sweat production is crucial for thermoregulation. However, sweating can be problematic for individuals with spinal cord injuries (SCI), as they display a blunting of sudomotor and vasomotor responses below the level of the injury. Sweat gland density and eccrine gland metabolism in SCI are not well understood. Consequently, this study examined sweat lactate (S-LA) (reflective of sweat gland metabolism), active sweat gland density (SGD), and sweat output per gland (S/G) in 7 SCI athletes and 8 able-bodied (AB) controls matched for arm ergometry VO2peak. A sweat collection device was positioned on the upper scapular and medial calf of each subject just prior to the beginning of the trial, with iodine sweat gland density patches positioned on the upper scapular and medial calf. Participants were tested on a ramp protocol (7 min per stage, 20 W increase per stage) in a common exercise environment (21±1°C, 45-65% relative humidity). An independent t-test revealed lower (p<0.05) SGD (upper scapular) for SCI (22.3 ±14.8 glands · cm−2) vs. AB. (41.0 ± 8.1 glands · cm−2). However, there was no significant difference for S/G between groups. S-LA was significantly greater (p<0.05) during the second exercise stage for SCI (11.5±10.9 mmol · l−1) vs. AB (26.8±11.07 mmol · l−1). These findings suggest that SCI athletes had less active sweat glands compared to the AB group, but the sweat response was similar (SLA, S/G) between AB and SCI athletes. The results suggest similar interglandular metabolic activity irrespective of overall sweat rate. 相似文献
109.
Aria Eshraghi Francisco J. Maldonado-Arocho Amandeep Gargi Marissa M. Cardwell Michael G. Prouty Steven R. Blanke Kenneth A. Bradley 《The Journal of biological chemistry》2010,285(24):18199-18207
Cytolethal distending toxins (CDTs) are tripartite protein exotoxins produced by a diverse group of pathogenic Gram-negative bacteria. Based on their ability to induce DNA damage, cell cycle arrest, and apoptosis of cultured cells, CDTs are proposed to enhance virulence by blocking cellular division and/or directly killing epithelial and immune cells. Despite the widespread distribution of CDTs among several important human pathogens, our understanding of how these toxins interact with host cells is limited. Here we demonstrate that CDTs from Haemophilus ducreyi, Aggregatibacter actinomycetemcomitans, Escherichia coli, and Campylobacter jejuni differ in their abilities to intoxicate host cells with defined defects in host factors previously implicated in CDT binding, including glycoproteins, and glycosphingolipids. The absence of cell surface sialic acid sensitized cells to intoxication by three of the four CDTs tested. Surprisingly, fucosylated N-linked glycans and glycolipids, previously implicated in CDT-host interactions, were not required for intoxication by any of the CDTs tested. Finally, altering host-cellular cholesterol, also previously implicated in CDT binding, affected intoxication by only a subset of CDTs tested. The findings presented here provide insight into the molecular and cellular basis of CDT-host interactions. 相似文献
110.
Sareth Rith C. Todd Davis Veasna Duong Borann Sar Srey Viseth Horm Savuth Chin Sovann Ly Denis Laurent Beat Richner Ikwo Oboho Yunho Jang William Davis Sharmi Thor Amanda Balish A. Danielle Iuliano San Sorn Davun Holl Touch Sok Heng Seng Arnaud Tarantola Reiko Tsuyuoka Amy Parry Nora Chea Lotfi Allal Paul Kitsutani Dora Warren Michael Prouty Paul Horwood Marc-Alain Widdowson Stephen Lindstrom Julie Villanueva Ruben Donis Nancy Cox Philippe Buchy 《Journal of virology》2014,88(23):13897-13909
Human infections with influenza A(H5N1) virus in Cambodia increased sharply during 2013. Molecular characterization of viruses detected in clinical specimens from human cases revealed the presence of mutations associated with the alteration of receptor-binding specificity (K189R, Q222L) and respiratory droplet transmission in ferrets (N220K with Q222L). Discovery of quasispecies at position 222 (Q/L), in addition to the absence of the mutations in poultry/environmental samples, suggested that the mutations occurred during human infection and did not transmit further. 相似文献