全文获取类型
收费全文 | 1259篇 |
免费 | 110篇 |
出版年
2021年 | 9篇 |
2019年 | 12篇 |
2017年 | 12篇 |
2016年 | 18篇 |
2015年 | 30篇 |
2014年 | 34篇 |
2013年 | 50篇 |
2012年 | 50篇 |
2011年 | 55篇 |
2010年 | 39篇 |
2009年 | 33篇 |
2008年 | 54篇 |
2007年 | 52篇 |
2006年 | 43篇 |
2005年 | 48篇 |
2004年 | 47篇 |
2003年 | 36篇 |
2002年 | 41篇 |
2001年 | 39篇 |
2000年 | 32篇 |
1999年 | 37篇 |
1998年 | 17篇 |
1997年 | 13篇 |
1996年 | 16篇 |
1995年 | 19篇 |
1994年 | 8篇 |
1993年 | 17篇 |
1992年 | 25篇 |
1991年 | 28篇 |
1990年 | 22篇 |
1989年 | 18篇 |
1988年 | 18篇 |
1987年 | 22篇 |
1986年 | 17篇 |
1985年 | 17篇 |
1984年 | 16篇 |
1983年 | 22篇 |
1982年 | 19篇 |
1981年 | 16篇 |
1980年 | 12篇 |
1979年 | 23篇 |
1978年 | 13篇 |
1977年 | 16篇 |
1976年 | 16篇 |
1975年 | 20篇 |
1974年 | 18篇 |
1973年 | 11篇 |
1972年 | 8篇 |
1969年 | 9篇 |
1968年 | 10篇 |
排序方式: 共有1369条查询结果,搜索用时 31 毫秒
31.
The immunological properties of the group B meningococcal alpha(2-8)-linked sialic acid polysaccharide have been rationalized in terms of a model where the random coil nature of the polymer can be described by the presence of local helices. The conformational versatility of the alpha NeuAc(2-8)alpha NeuAc linkage has been explored by NMR studies at 600 MHz in conjunction with potential energy calculations for colominic acid, an alpha(2-8)NeuAc polymer, and the trisaccharide alpha NeuAc(2-8)alpha NeuAc(2-8)beta NeuAc. Potential energy calculations were used to estimate the energetically favorable conformers and to describe the wide range of helices which the polymer can adopt. No unique conformer was found to satisfy all NMR constraints, and only ensemble averaged nuclear Overhauser enhancements could correctly simulate the experimental data. Conformational differences between the polymer and the trisaccharide could be best explained in terms of slight changes in the relative distribution of conformers in solution. Similar helical parameters for the alpha(2-8)NeuAc polymer and poly(A) were proposed as the basis for their cross-reactivity to a monoclonal antibody IgMNOV. The unusual length dependency for binding of oligosaccharide to group B specific antibodies was postulated to arise from the recognition of a high-order local helix with an extended conformation which was not highly populated in solution. 相似文献
32.
33.
Temperature and chemical shocks induce chilling tolerance in germinating Cucumis sativus (cv. Poinsett 76) seeds 总被引:3,自引:0,他引:3
Roots of 24-h-old germinated cucumber ( Cucumis sativus cv. Poinsett 76) seeds were subjected to thermal and chemical stresses, equilibrated at 25°C for 2 h and chilled at 2.5°C for 96 h. The germinated seeds were then held at 25°C for 72 h after they were chilled and the elongation of the primary root was used as a measure of chilling tolerance. Control roots elongated from an initial length of 0.2 cm to a final length of 6.3 cm at the end of 72 h. while chilled roots elongated to a final length of only 0.4 to 0.6 cm. Exposure to 0.4 M ethanol for 4 h or to 40°C for 1 h induced substantial chilling tolerance and the roots had a final length of 4.1 and 3.1 cm. respectively. Exposure to 7.5°C for 3 h conferred less chilling tolerance (elongation to 1.4 cm). while exposure to other chemicals (i.e. aqueous solutions of Ca(NO3 )2 , mannitol. methanol and NaCl) produced less, though still significant increases in chilling tolerance. A more severe chilling treatment of 144 h at 2.5°C was required to consistently induce elevated rates of ion leakage. Only the heat and the ethanol shock treatments significantly reduced chilling-induced ion leakage. Inclusion of the protein synthesis inhibitor cycloheximide negated the protective effects of these shock treatments. It appears that de novo protein synthesis is required for induction of chilling tolerance by a variety of chemical and thermal shock treatments. 相似文献
34.
Enzymological and mutational analysis of a complex primary hyperoxaluria type 1 phenotype involving alanine:Glyoxylate aminotransferase peroxisome-to-mitochondrion mistargeting and intraperoxisomal aggregation 总被引:6,自引:1,他引:5
下载免费PDF全文
![点击此处可从《American journal of human genetics》网站下载免费的PDF全文](/ch/ext_images/free.gif)
C. J. Danpure P. E. Purdue P. Fryer S. Griffiths J. Allsop M. J. Lumb K. M. Guttridge P. R. Jennings J. I. Scheinman S. M. Mauer N. O. Davidson 《American journal of human genetics》1993,53(2):417-432
Primary hyperoxaluria type 1 (PH1) is a rare autosomal recessive disease caused by a deficiency of the liver-specific peroxisomal enzyme alanine:glyoxylate aminotransferase (AGT). Three unrelated PH1 patients, who possess a novel complex phenotype, are described. At the enzymological level, this phenotype is characterized by a complete, or nearly complete, absence of AGT catalytic activity and reduced AGT immunoreactivity. Unlike normal individuals in whom the AGT is confined to the peroxisomal matrix, the immunoreactive AGT in these three patients was distributed approximately equally between the peroxisomes and mitochondria. The peroxisomal AGT appeared to be aggregated into amorphous core-like structures in which no other peroxisomal enzymes could be identified. Mutational analysis of the AGT gene showed that two of the three patients were compound heterozygotes for two previously unrecognized point mutations which caused Gly41→Arg and Phe152→Iso amino acid substitutions. The third patient was shown to be a compound heterozygote for the Gly41→Arg mutation and a previously recognized Gly170→Arg mutation. All three patients were homozygous for the Pro11→Leu polymorphism that had been found previously with a high allelic frequency in normal populations. It is suggested that the Phe152→Iso and Gly170→Arg substitutions, which are only eighteen residues apart and located in the same highly conserved internal region of 58 amino acids, might be involved in the inhibition of peroxisomal targeting and/or import of AGT and, in combination with the Pro11→Leu polymorphism, be responsible for its aberrant mitochondrial compartmentalization. On the other hand, the Gly41→Arg substitution, either in combination with the Pro11→Leu polymorphism or by itself, is predicted to be responsible for the intraperoxisomal aggregation of the AGT protein. 相似文献
35.
36.
Michael P. Jennings Peter van der Ley Kathy E. Wilks Duncan J. Maskell † Jan T. Poolman E. Richard Moxon 《Molecular microbiology》1993,10(2):361-369
The galE gene from Haemophilus influenzae was used as a hybridization probe for the galE gene of Neisseria meningitidis Group B, identifying two different homologous loci. Each of the loci was cloned and nucleotide sequence analysis revealed that both loci contained sequences similar to galE. One contained a functional galE gene and mapped to the capsule biosynthetic locus. The second contained only a partial galE-coding sequence, which did not express a functional gene product. A galE mutant meningococcal strain was constructed by transformation with an inactivated galE gene. Analysis of the LPS from the galE mutant strain revealed an apparent reduction in molecular weight and a loss of reactivity with monoclonal antibodies specific for structures known to contain galactose. These results are consistent with an essential role for galE in the incorporation of galactose into meningococcal lipopolysaccharide. 相似文献
37.
38.
39.
Administration of a newly discovered second atrial peptide, iso-atrial natriuretic peptide (or iso-rANP(1-45) for the rat), caused hypotension, decreased heart rate, diuresis, and increased renal excretion of Na+, K+, and Cl- in the anesthetized rat. Bolus injections of chemically synthetic iso-rANP(1-45) had circulatory and diuretic activity equal to or greater than rANP(99-126) but, at low doses, a lesser effect on renal electrolyte excretion. The synthetic peptide fragment, iso-rANP(17-45), analogous in structure to rANP(99-126), had attenuated activity on the circulation, and at low doses, attenuated activity on the kidney. At higher doses, where renal responses to rANP(99-126) were less (downside of a biphasic response), both iso-rANP(1-45) and (17-45) had greater effects on water and electrolyte excretion than rANP(99-126). Injections of iso-rANP(1-45) and (17-45) increased hematocrit, whereas rANP(99-126) did not; furthermore, unlike rANP(99-126), iso-rANP did not affect arterial plasma Na+ concentration. The heart produces at least two genetically different atrial natriuretic peptides which affect the circulation and salt and water balance. 相似文献
40.
Identification of a locus involved in meningococcal lipopolysaccharide biosynthesis by deletion mutagenesis 总被引:4,自引:0,他引:4
Peter van der Ley Marco Kramer Liana Steeghs Betsy Kuipers Svein R. Andersen Michael P. Jennings E. Richard Moxon & Jan T. Poolman 《Molecular microbiology》1996,19(5):1117-1125
A novel method for insertion/deletion mutagenesis in meningococci was devised. This consisted of ligating a digest of total chromosomal DNA to a 1.1 kb restriction fragment containing an erythromycin-resistance marker ( ermC ), and subsequent transformation of the ligation mixture into the homologous meningococcal strain H44/76. Southern blotting of a number of the resulting erythromycin-resistant transformants demonstrated that all carried the ermC gene inserted at different positions in the chromosome. Mutants with a specific phenotype were identified by screening with the anti-lipopolysaccharide (LPS) monoclonal antibody MN4A8B2, which is specific for immunotype L3. In this way, two independent L3-negative mutant strains were isolated. In transformation experiments with chromosomal DNA from these mutants, erythromycin-resistance and lack of MN4A8B2 reactivity were always linked, showing that the insertion/deletion was in a locus involved in LPS biosynthesis. On SDS–PAGE, the mutant LPS displayed an electrophoretic mobility intermediate between that produced by the previously isolated galE and rfaF mutant strains. Chemical analysis of the mutant LPS revealed that the structure was probably lipid A–(KDO)2 –(Hep)2 . Chromosomal DNA flanking the ermC insertion in these two mutant strains was cloned, and used as probe for the isolation of the corresponding region of the wild-type strain. From hybridization and polymerase chain reaction (PCR) analysis, it could be concluded that both mutations map to the same locus. The affected gene probably encodes the glycosyltransferase necessary for adding N -acetylglucosamine to heptose. 相似文献