全文获取类型
收费全文 | 363篇 |
免费 | 42篇 |
专业分类
405篇 |
出版年
2021年 | 5篇 |
2020年 | 5篇 |
2019年 | 5篇 |
2017年 | 8篇 |
2016年 | 14篇 |
2015年 | 19篇 |
2014年 | 18篇 |
2013年 | 14篇 |
2012年 | 17篇 |
2011年 | 15篇 |
2010年 | 12篇 |
2009年 | 12篇 |
2008年 | 12篇 |
2007年 | 8篇 |
2006年 | 8篇 |
2005年 | 9篇 |
2004年 | 11篇 |
2003年 | 6篇 |
2002年 | 5篇 |
2001年 | 8篇 |
2000年 | 13篇 |
1999年 | 14篇 |
1998年 | 10篇 |
1997年 | 10篇 |
1996年 | 11篇 |
1995年 | 6篇 |
1994年 | 4篇 |
1992年 | 4篇 |
1991年 | 5篇 |
1990年 | 4篇 |
1989年 | 4篇 |
1988年 | 5篇 |
1987年 | 7篇 |
1986年 | 6篇 |
1985年 | 7篇 |
1984年 | 8篇 |
1983年 | 6篇 |
1982年 | 5篇 |
1981年 | 5篇 |
1980年 | 6篇 |
1979年 | 6篇 |
1978年 | 5篇 |
1977年 | 4篇 |
1976年 | 5篇 |
1975年 | 4篇 |
1974年 | 4篇 |
1973年 | 7篇 |
1971年 | 2篇 |
1969年 | 4篇 |
1965年 | 2篇 |
排序方式: 共有405条查询结果,搜索用时 15 毫秒
1.
Changes in the duration and size of the vulnerable period of the myocardium in the presence of respiratory changes were studied in acute experiments on rats. The limits of the vulnerable period were determined by directly stimulating the heart during ventilation via the enlarged respiratory dead space, during hyperventilation and during heart failure. In the control group (normal ventilation without enlargement of the dead space), the vulnerable period lasted 5.7 +/- 0.76 ms. During ventilation via the enlarged dead space, hypercapnic hypoxaemia developed and the vulnerable period was markedly prolonged (18.55 +/- 5.29 ms) by a shift of its inner limit to the left. Hyperventilation caused normoxic to hyperoxic hypocapnia and markedly reduced the duration of the vulnerable period (8.17 +/- 2.21 and 9.31 +/- 2.38 ms respectively). The vulnerable period lengthened the most in heart failure (25.46 +/- 3.93), mainly as a result of a shift of its outer limit. In all the experimental groups there was a shift of the vulnerable period to the right, which was fastest in hypercapnic hypoxaemia and slowest in hyperoxic hypocapnia. The administration of Inderal (3 mg/kg i.p.) or Arfonad (50 mg/kg i.p.) markedly shortened the vulnerable period during hypercapnic hypoxaemia (9.87 +/- 2.78 and 9.32 +/- 2.16 ms respectively), but did not block the shift. Lengthening of the vulnerable period during hypercapnic hypoxaemia was probably due to activation of sympathetic nerves via beta-adrenergic receptors. 相似文献
2.
"In solution" synthesis and separation of diastereoisomers of 5'-O-(4,4'-dimethoxytriphenylmethyl)dithymidyl (3',5') 4,4'-dimethoxytriphenylmethanephosphonate (DMTTDMTT) is described. One of diastereoisomers was successfully crystallized and characterized by means of HPLC. 相似文献
3.
W Niewiarowski Z J Le?nikowski A Wilk P Guga A Okruszek B Uznański W Stec 《Acta biochimica Polonica》1987,34(2):217-231
Diastereomers of the title compound were obtained and absolute configuration was assigned by means of stereochemical correlation. Their reaction with 3'-O-methoxyacetylthymidine in the presence of triisopropylbenzenesulphonyl (4-nitro) triazole is neither chemo- nor stereo-selective and leads to diastereomeric pairs of dithymidyl (3',5')methanephosphonate and -methanephosphonothioate. Obtained results are discussed in terms of mechanism of activation of phosphodiesters under conditions known as "phosphotriester approach to oligonucleotide synthesis". 相似文献
4.
The isopropoxyacetic group for convenient base protection during solid-support synthesis of oligodeoxyribonucleotides and their triester analogs. 总被引:2,自引:2,他引:0 下载免费PDF全文
Isopropoxyacetic anhydride was successfully used for protection of exoaminofunctions of 2'-deoxyadenosine, -guanosine and -cytidine. N-isopropoxyacetylated nucleosides are stable under the conditions of the synthesis of oligodeoxyribonucleotides on the solid support. Removal of N-isopropoxyacetyl is much faster than that of commonly used benzoyl or isobutyryl groups viz. it is completed within the operation of cleavage of the oligodeoxyribonucleotide from the solid support. This observation enabled synthesis of -OCH2CH3 and -OCH2CF3 triesters, which hydrolyse partially or completely when standard deprotection conditions are applied. 相似文献
5.
R Kubica B Nielsen A Bonnesen I B Rasmussen J Stok?osa B Wilk 《Acta physiologica Polonica》1983,34(5-6):569-579
Plasma volume was decreased by prolonged bicycle exercise, by passive heating in warm water, by sauna dehydration, and by diuretically induced dehydration in eleven well trained subjects. Blood samples from an arm vein were taken before and after this pre-treatment, as well as after a subsequent standard exercise test (SET) on a bicycle ergometer (50%, 70% and 105% of max VO2; the SET with no pre-treatment was used as a control condition. The changes in plasma concentration of Na+, K+ and Cl- were not proportional to the calculated plasma volume changes. The Na+ and Cl- concentrations always increased in the plasma, while plasma potassium concentration was increased after prolonged exercise, but decreased after the other types of dehydrations. The standard exercise test produced a pronounced fall in total calculated plasma potassium and in K+ concentration measured 3-5 min after exercise in all types of experiments. In the standard exercise test the calculated water loss from the plasma volume was relatively large. It amounted to about 2/3 of the total water loss in the standard exercise test and was independent of the pre-treatments. 相似文献
6.
Marian Orlowski Elizabeth Wilk Stevens Pearce Sherwin Wilk 《Journal of neurochemistry》1979,33(2):461-469
Abstract— An enzyme with the specificity of a prolyl endopeptidase was purified about 880-fold from rabbit brain. The enzyme hydrolyzes peptidylprolyl-peptide and peptidylprolyl-amino acid bonds. Several biologically active peptides such as angiotensin, bradykinin, neurotensin. substance P and thyrotropin releasing hormone are degraded by hydrolysis of the bond between the carboxyl group of proline and the adjacent amino acid or ammonia respectively. The enzyme is activated by dithiothreitol and inhibited by heavy metals and thiol blocking agents. The serine protease inhibitor phenylmethanesulfonylfluoride has no effect on activity; however, inhibition was obtained with diisopropylfluorophosphate. Prolyl endopeptidase has a molecular weight of about 66,000 and a pH optimum of about 8.3. A new chromogenic substrate, N -benzyloxycarbonylglycyl-L-prolylsulfamethoxazole, was used for determination of enzyme activity. The substrate is hydrolyzed to N -benzyloxycarbonylglycyl-L-proline and free sulfamethoxazole which can be conveniently determined by a colorimetric procedure. 相似文献
7.
Metabolism of gamma-glutamyl amino acids and peptides in mouse liver and kidney in vivo. 总被引:1,自引:0,他引:1
The metabolism in vivo of gamma-glutamyl amino acids and peptides was studied in the mouse after administration of loading doses of L-gamma-glutamyl-2-aminobutyrate and several other gamma-glutamyl compounds, including glutathione. A great and rapid accumulation of glutamate, glutamine, aspartate and pyrrolidone carboxylate was observed in the kidney. Similarly, after administration of a tracer dose of L-gamma-[14C]glutamyl-L-2-aminobutyrate a rapid incorporation of label into kidney glutamate, glutamine and aspartate was found. These results suggest that both the hydrolytic and gamma-glutamyl transfer reactions catalyzed by gamma-glutamyl transpeptidase are active in the renal handling of gamma-glutamyl compounds. Indirect evidence was obtained that L-gamma-glutamyl-2-aminobutyrate is partially taken up by the kidney cell in an intact form. In contrast to the kidney, administration of several gamma-glutamyl derivatives did not cause an increase in liver glutamate, glutamine and pyrrolidone carboxylate. After administration of L-gamma-glutamyl-2-aminobutyrate only a slight increase in liver aspartate and pyrrolidone carboxylate was observed. Experiments with L-gamma-[14C]glutamyl-L-2-aminobutyrate suggest that this derivative is largely first degraded to its component amino acids (probably in the kidney) before entering into the metabolism of the liver cell. gamma-Glutamyl transpeptidase may function in the metabolism and transport of glutathione and other gamma-glutamyl compounds in a manner analogous to the function of dipeptidases and disaccharidases in the metabolism and transport of dipeptides and disaccharides respectively. 相似文献
8.
Gas chromatographic methods for the quantitation of pyrrolidone carboxylate and γ-glutamyl amino acids are described. These intermediates of the γ-glutamyl cycle were separated by ion exchange chromatography and converted to their N-acyl-ester derivatives in a reaction with a mixture of 2,2,3,3,3-pentafluoro-1-propanol and pentafluoropropionic anhydride. The derivatives have excellent electron capture properties thus making possible their determination even in small amounts of material of biological origin. The method was applied for the determination of concentrations of pyrrolidone carboxylate in human urine and cerebrospinal fluid, and in the brain, liver, and kidney of the mouse. It was also used to demonstrate the formation in mouse tissues of several γ-glutamyl derivatives of amino acids after administration of the corresponding free amino acid. 相似文献
9.
Subcellular Distribution of Prolyl Endopeptidase and Cation-Sensitive Neutral Endopeptidase in Rabbit Brain 总被引:1,自引:5,他引:1
Karl Dresdner Louis A. Barker Marian Orlowski Sherwin Wilk 《Journal of neurochemistry》1982,38(4):1151-1154
Abstract: The subcellular distribution of prolyl endopeptidase, and of cationsensitive neutral endopeptidase, two enzymes actively metabolizing many neuropeptides, was determined in homogenates of rabbit brain. The subcellular distribution of both enzymes was more similar to lactate dehydrogenase, a cytoplasmic enzyme marker, than to choline acetyltransferase, a synaptosomal marker. Only 35% of the activity of these two neutral endopeptidases was found in the crude mitochondrial fraction (P2 ), the bulk of the remaining activity being associated with the high-speed supernatant. Prolyl endopeptidase and cation-sensitive neutral endopeptidase thus can be regarded as mainly cytoplasmic enzymes in the rabbit brain. 相似文献
10.
Genomewide association study for susceptibility genes contributing to familial Parkinson disease 总被引:1,自引:0,他引:1
Pankratz N Wilk JB Latourelle JC DeStefano AL Halter C Pugh EW Doheny KF Gusella JF Nichols WC Foroud T Myers RH;PSG-PROGENI GenePD Investigators Coordinators Molecular Genetic Laboratories 《Human genetics》2009,124(6):593-605
Five genes have been identified that contribute to Mendelian forms of Parkinson disease (PD); however, mutations have been
found in fewer than 5% of patients, suggesting that additional genes contribute to disease risk. Unlike previous studies that
focused primarily on sporadic PD, we have performed the first genomewide association study (GWAS) in familial PD. Genotyping
was performed with the Illumina HumanCNV370Duo array in 857 familial PD cases and 867 controls. A logistic model was employed
to test for association under additive and recessive modes of inheritance after adjusting for gender and age. No result met
genomewide significance based on a conservative Bonferroni correction. The strongest association result was with SNPs in the
GAK/DGKQ region on chromosome 4 (additive model: p = 3.4 × 10−6; OR = 1.69). Consistent evidence of association was also observed to the chromosomal regions containing SNCA (additive model: p = 5.5 × 10−5; OR = 1.35) and MAPT (recessive model: p = 2.0 × 10−5; OR = 0.56). Both of these genes have been implicated previously in PD susceptibility; however, neither was identified in
previous GWAS studies of PD. Meta-analysis was performed using data from a previous case–control GWAS, and yielded improved
p values for several regions, including GAK/DGKQ (additive model: p = 2.5 × 10−7) and the MAPT region (recessive model: p = 9.8 × 10−6; additive model: p = 4.8 × 10−5). These data suggest the identification of new susceptibility alleles for PD in the GAK/DGKQ region, and also provide further support for the role of SNCA and MAPT in PD susceptibility.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.
N. Pankratz and J. B. Wilk are joint first authors. 相似文献