全文获取类型
收费全文 | 576篇 |
免费 | 56篇 |
出版年
2022年 | 3篇 |
2021年 | 5篇 |
2018年 | 3篇 |
2017年 | 4篇 |
2016年 | 7篇 |
2015年 | 18篇 |
2014年 | 16篇 |
2013年 | 25篇 |
2012年 | 19篇 |
2011年 | 26篇 |
2010年 | 27篇 |
2009年 | 27篇 |
2008年 | 25篇 |
2007年 | 37篇 |
2006年 | 23篇 |
2005年 | 26篇 |
2004年 | 18篇 |
2003年 | 27篇 |
2002年 | 16篇 |
2001年 | 20篇 |
2000年 | 16篇 |
1999年 | 15篇 |
1998年 | 20篇 |
1997年 | 3篇 |
1995年 | 8篇 |
1994年 | 12篇 |
1993年 | 5篇 |
1992年 | 20篇 |
1991年 | 14篇 |
1990年 | 10篇 |
1989年 | 6篇 |
1988年 | 5篇 |
1987年 | 11篇 |
1986年 | 7篇 |
1985年 | 8篇 |
1984年 | 13篇 |
1983年 | 6篇 |
1982年 | 7篇 |
1981年 | 9篇 |
1980年 | 6篇 |
1979年 | 9篇 |
1977年 | 4篇 |
1976年 | 6篇 |
1975年 | 2篇 |
1974年 | 2篇 |
1973年 | 3篇 |
1970年 | 3篇 |
1969年 | 2篇 |
1968年 | 2篇 |
1957年 | 2篇 |
排序方式: 共有632条查询结果,搜索用时 31 毫秒
1.
K P Ossenkopp M Kavaliers F S Prato G C Teskey E Sestini M Hirst 《Life sciences》1985,37(16):1507-1514
Adult male mice exposed to a Nuclear Magnetic Resonance Imaging (NMRI) procedure during the mid-dark period and injected with morphine (10 mg/kg) failed to exhibit the normal nocturnally enhanced morphine analgesia response to a thermal stimulus that was displayed by mice exposed to a sham imaging procedure and treated with morphine (p less than .01). When tested during the mid-light period, animals exposed to the NMRI procedure and given morphine displayed attenuated analgesia levels relative to sham exposed mice (p less than .01) treated with morphine. However, the morphine induced analgesia was not totally abolished since the imaged mice still exhibited analgesia relative to saline treated mice (p less than .01). These results suggest that the magnetic and/or radio-frequency fields associated with the NMRI procedure alter both day- and night-time responses to morphine. These results may reflect magnetic field induced alterations in neuronal calcium binding and/or alterations in nocturnal pineal gland activity. 相似文献
2.
3.
George K. Hirst 《BMJ (Clinical research ed.)》1962,1(5290):1431-1437
4.
Cardiomegaly was observed in rats severely intoxicated with ethanol for a 4 day period. It was apparent at 48 hours of treatment, a time at which cardiac protein was elevated and continued into withdrawal. During a 4 day abstinence period the degree of hypertrophy declined towards normal. Cardiac noradrenaline was reduced at the 48 hour time of intoxication, then increased gradually in the further experimental period. As the cardiac hypertrophy occurs at a time that urinary catecholamines are elevated and the adrenal medulla is intensely stimulated, it is proposed that increased levels of circulating catecholamines are largely responsible for the enlargement of the heart. 相似文献
5.
Alterations at the carboxyl terminus change assembly and secretion properties of the B subunit of Escherichia coli heat-labile enterotoxin 总被引:12,自引:0,他引:12 下载免费PDF全文
The gene encoding the B subunit of heat-labile enterotoxin (etxB) was mutated at its 3' end by targeted addition of random nucleotide sequences. Gene products from five mutated etxB genes, all of which were shown to encode B subunits with short carboxy-terminal amino acid extensions, were analyzed with respect to a range of functional and structural properties. One class of altered B subunits, exemplified by EtxB124 and EtxB138, which both have seven extra amino acid residues, were found to be specifically defective in their ability to stably associate with A subunits and form holotoxin. Other altered B subunits were less subtlely affected by extensions at their C termini and were, in addition to their failure to associate with A subunits, unable to translocate into the periplasm of Escherichia coli, to pentamerize, or to bind to GM1 ganglioside. This suggests that the carboxy-terminal domain of EtxB mediates A subunit-B subunit interaction. 相似文献
6.
Cellular retinoic acid-binding protein and the role of retinoic acid in the development of the chick embryo 总被引:7,自引:0,他引:7
The distribution of cellular retinoic acid-binding protein (CRABP) in four stages of chick development is described using an affinity-purified antibody against rat CRABP. CRABP is the protein to which retinoic acid (RA) binds when it enters cells and may reflect the requirement of those cells for RA. We found several discrete cell populations which showed high levels of immunoreactivity. Some were in the neural tube such as the commissural neurons and the dorsal roof plate. Some were of neural crest origin such as the dorsal root ganglia, sensory axons, sympathetic ganglia, and enteric ganglia. The remaining populations were certain connective tissue cells, limb bud cells, and the myotome. These results suggest that certain organ systems, particularly the nervous system, have a requirement for RA during development and they may further our understanding of the teratogenic effects of retinoids on the embryo. 相似文献
7.
Mapping of FMR1, the gene implicated in fragile X-linked mental retardation, on the mouse X chromosome 总被引:2,自引:0,他引:2
A genetic map of the Cf-9 to Dmd region of the mouse X chromosome has been established by typing 100 offspring from a Mus musculus x Mus spretus interspecific backcross for the four loci Cf-9, Cdr, Gabra3, and Dmd. The following order and genetic distances in centimorgans were determined: (Cf-9)-2.4 +/- 1.7-(Cdr)-2.0 +/- 1.4-(Gabra3)-4.1 +/- 2.0-(Dmd). Six backcross offspring carrying X chromosomes with recombination events in the Cdr-Dmd region were identified. These recombination events were used to define the position of Fmr-1, the murine homologue of FMR1, which is the gene implicated in the fragile X syndrome in man, and that of DXS296h, the murine homologue of DXS296. Both Fmr-1 and DXS296h were mapped into the same recombination interval as Gabra3 on the mouse X chromosome. These findings provide strong support for the concept that the order of loci lying in the Cf-9 to Gabra3 segment of the X chromosome is highly conserved between human and mouse. 相似文献
8.
A homologue of the Escherichia coli DsbA protein involved in disulphide bond formation is required for enterotoxin biogenesis in Vibrio cholerae 总被引:22,自引:0,他引:22
A strain of Vibrio cholerae, which had been engineered to express high levels of the non-toxic B subunit (EtxB) of Escherichia coli heat-labile enterotoxin, was subjected to transposon (TnphoA) mutagenesis. Two chromosomal TnphoA insertion mutations of the strain were isolated that showed a severe defect in the amount of EtxB produced. The loci disrupted by TnphoA in the two mutant derivatives were cloned and sequenced, and this revealed that the transposon had inserted at different sites in the same gene. The open reading frame of the gene predicts a 200-amino-acid exported protein, with a Cys-X-X-Cys motif characteristic of thioredoxin, protein disulphide isomerase, and DsbA (a periplasmic protein required for disulphide bond formation in E. coli). The V. cholerae protein exhibited 40% identity with the DsbA protein of E. coli, including 90% identity in the region of the active-site motif. Introduction of a plasmid encoding E. coli DsbA into the V. cholerae TnphoA derivatives was found to restore enterotoxin formation, whilst expression of Etx or EtxB in a dsbA mutant of E. coli confirmed that DsbA is required for enterotoxin formation in E. coli. These results suggest that, since each EtxB subunit contains a single intramolecular disulphide bond, a transient intermolecular interaction with DsbA occurs during toxin subunit folding which catalyses formation of the disulphide in vivo. 相似文献
9.
10.
M C Hirst K Rack Y Nakahori A Roche M V Bell G Flynn Z Christadoulou R N MacKinnon M Francis A J Littler 《Nucleic acids research》1991,19(12):3283-3288
The fragile X syndrome is a common cause of mental retardation and is associated with a fragile site at Xq27.3 (FRAXA). Recently, evidence has been presented for the role of methylation and genomic imprinting in the expression of the disease. We have identified a site of methylation in patients by long range restriction mapping of the region. In this paper we present a YAC contig of this area, localise the CpG sequences which are methylated, and show by in situ hybridisation that the site of fragility lies within this region. 相似文献