首页 | 本学科首页   官方微博 | 高级检索  
文章检索
  按 检索   检索词:      
出版年份:   被引次数:   他引次数: 提示:输入*表示无穷大
  收费全文   1095篇
  免费   63篇
  2023年   2篇
  2022年   11篇
  2021年   28篇
  2020年   9篇
  2019年   21篇
  2018年   14篇
  2017年   21篇
  2016年   25篇
  2015年   54篇
  2014年   57篇
  2013年   74篇
  2012年   77篇
  2011年   103篇
  2010年   56篇
  2009年   43篇
  2008年   67篇
  2007年   79篇
  2006年   55篇
  2005年   61篇
  2004年   59篇
  2003年   44篇
  2002年   47篇
  2001年   11篇
  2000年   9篇
  1999年   14篇
  1998年   9篇
  1997年   11篇
  1996年   5篇
  1995年   2篇
  1994年   4篇
  1993年   2篇
  1992年   12篇
  1991年   8篇
  1990年   6篇
  1989年   4篇
  1988年   3篇
  1985年   3篇
  1983年   4篇
  1982年   6篇
  1981年   2篇
  1979年   4篇
  1977年   2篇
  1973年   4篇
  1972年   5篇
  1970年   2篇
  1969年   2篇
  1968年   2篇
  1967年   5篇
  1966年   3篇
  1965年   3篇
排序方式: 共有1158条查询结果,搜索用时 15 毫秒
991.
Using a known dual PPARalpha/gamma activator (5) as a structural template, SAR evaluations led to the identification of triple PPARalpha/gamma/delta activators (18-20) with equal potency and efficacy on all three receptors. These compounds could become useful tools for studying the combined biological effects of PPARalpha/gamma/delta activation.  相似文献   
992.
It has recently been reported that the mode of inheritance of body height, weight and BMI in five ethnically and geographically different populations can be described in terms of a major gene (MG) model. Here, using the pedigree sample from the island populations of Middle Dalmatia, Croatia (1,312 observed individuals in 462 pedigrees), the evidence is presented that supports the above findings. By applying the usual transmission probability tests, the hypothesis has been accepted that a significant part of the variation of each one of those three basic morphological traits can be attributed to the effect of a putative large-effect gene. The effect of a putative MG is responsible for 39-50% of age and sex adjusted trait's variation and for 34-48% of the total (non age-adjusted) variation of height, weight and BMI.  相似文献   
993.
This study aims at determining the mean value of the ophthalmic anthropometrics parametar-IPD (Interpupillary distance) and the mean value of NC/D (Near convergence/distance) in 300 subjects aged 5 to 60 years. The influence of IPD on the NC/D ratio in the same subjects will also be investigated. The investigation showed that the mean value of IPD is 60.5 +/- 2.4 cm, and the mean value of NC/D ratio is 4.95 +/- 2.28 prD. Mean IPD of 5.1 cm in 5-year old children increases to 6.3 cm in adult over 20. In adulthood, IPD remains the same, i.e. 6.3 cm. Our study showed that the NC/D ratio is stable during lifetime. Since NC/D is stabile and IPD changes during lifetime, it is evident that factors other than IPD, such as convergence and accommodation, influence the stability of the NC/D ratio.  相似文献   
994.
The caseins of milk form a unique calcium–phosphate transport complex that provides these necessary nutrients to the neonate. The colloidal stability of these particles is primarily the result of -casein. As purified from milk, this protein occurs as spherical particles with a weight average molecular weight of 1.18 million. The protein exhibits a unique disulfide bonding pattern, which (in the absence of reducing agents) ranges from monomer to octamers and above on SDS-PAGE. Severe heat treatment of the -casein (90°C) in the absence of SDS, before electrophoresis, caused an increase in the polymeric distribution: up to 40% randomly aggregated high–molecular weight polymers, presumably promoted by free sulfhydryl groups (J. Protein Chem. 17: 73–84, 1998). To ascertain the role of the sulfhydryl groups, the protein was reduced and carboxymethylated (RCM-). Surprisingly, at only 37°C, the RCM--casein exhibited an increase in weight average molecular weight and tendency to self-association when studied at 3000 rpm by analytical ultracentrifugation. Electron microscopy (EM) of the 37°C RCM sample showed that, in addition to the spherical particles found in the native protein, there was a high proportion of fibrillar structures. The fibrillar structures were up to 600 nm in length. Circular dichroism (CD) spectroscopy was used to investigate the temperature-induced changes in the secondary structure of the native and RCM--caseins. These studies indicate that there was little change in the distribution of secondary structural elements during this transition, with extended strand and turns predominating. On the basis of three-dimensional molecular modeling predictions, there may exist a tyrosine-rich repeated sheet-turnsheet motif in -casein (residues 15–65), which may allow for the stacking of the molecules into fibrillar structures. Previous studies on amyloid proteins have suggested that such motifs promote fibril formation, and near-ultraviolet CD and thioflavin-T binding studies on RCM--casein support this concept. The results are discussed with respect to the role that such fibrils may play in the synthesis and secretion of casein micelles in lactating mammary gland.  相似文献   
995.
The caseins of milk form a unique calcium–phosphate transport complex that provides these necessary nutrients to the neonate. The colloidal stability of these particles is primarily the result of κ-casein. As purified from milk, this protein occurs as spherical particles with a weight average molecular weight of 1.18 million. The protein exhibits a unique disulfide bonding pattern, which (in the absence of reducing agents) ranges from monomer to octamers and above on SDS-PAGE. Severe heat treatment of the κ-casein (90°C) in the absence of SDS, before electrophoresis, caused an increase in the polymeric distribution: up to 40% randomly aggregated high–molecular weight polymers, presumably promoted by free sulfhydryl groups (J. Protein Chem. 17: 73–84, 1998). To ascertain the role of the sulfhydryl groups, the protein was reduced and carboxymethylated (RCM-κ). Surprisingly, at only 37°C, the RCM-κ-casein exhibited an increase in weight average molecular weight and tendency to self-association when studied at 3000 rpm by analytical ultracentrifugation. Electron microscopy (EM) of the 37°C RCM sample showed that, in addition to the spherical particles found in the native protein, there was a high proportion of fibrillar structures. The fibrillar structures were up to 600 nm in length. Circular dichroism (CD) spectroscopy was used to investigate the temperature-induced changes in the secondary structure of the native and RCM-κ-caseins. These studies indicate that there was little change in the distribution of secondary structural elements during this transition, with extended strand and κ turns predominating. On the basis of three-dimensional molecular modeling predictions, there may exist a tyrosine-rich repeated sheet-turnsheet motif in κ-casein (residues 15–65), which may allow for the stacking of the molecules into fibrillar structures. Previous studies on amyloid proteins have suggested that such motifs promote fibril formation, and near-ultraviolet CD and thioflavin-T binding studies on RCM-κ-casein support this concept. The results are discussed with respect to the role that such fibrils may play in the synthesis and secretion of casein micelles in lactating mammary gland.  相似文献   
996.
Oja T 《Hereditas》2002,137(2):113-118
Allozyme variation of ten heterozymes of seven enzymes among five accessions of a rare diploid Bromus fasciculatus was analysed with the use of PAGE and compared with that for six other species of section Genea of the genus Bromus. Allozymes charasteristic for diploids B. tectorum and B. fasciculatus are combined in fixed heterozygous phenotypes of tetraploid B. rubens. Fixed heterozygous phenotypes of tetraploid B. madritensis combine one allozyme of B. fasciculatus with another of diploid B. sterilis at each of the loci studied. Of the three diploids studied, only B. sterilis fits well for a role of a genome donor for the polyploid B. diandrus-rigidus complex. Bromus fasciculatus thus appears to be a diploid ancestor for the two tetraploids of section Genea, B. rubens and B. madritensis.  相似文献   
997.
Peusha H  Lebedeva T  Priilinn O  Enno T 《Hereditas》2002,136(3):201-206
Genetic studies using monosomic and hybridological analyses had confirmed that resistance of a common wheat line k-15560 to powdery mildew in seedling stage was conditioned by one dominant gene located on chromosome 7B, and resistance in adult stage was controlled by two dominant genes. Cytological analysis of meiosis in the F1 monosomic hybrids has revealed reciprocal translocation involving chromosomes 2A/7A. In the F1 monosomic hybrids genes, causing a decrease in pairing were found on chromosomes 3B and 4D, and genes enhancing pairing--on chromosomes 2A and 3A.  相似文献   
998.
Previously, we have shown that a phosphorothioate antisense oligonucleotide (ODN) targeted against c-raf RNA (ISIS5132; cRaf-AS) induces apoptosis in human tumor cells. We now show that the same ODN also efficiently triggers apoptosis in human tumor xenografts in nu/nu mice. Although cRaf-AS showed a clearly inhibitory effect on the growth of established tumors (approximately 150 mm3) compared to a mismatched control ODN (MM), tumor progression was not prevented. This correlated with a partial refractoriness of the tumor to cRaf-AS-induced cell killing, which seemed to be due to an inhomogeneous and inefficient penetration of the ODN into the tumor tissue rather than cellular resistance. In agreement with this conclusion, we found that growth of small tumors (<50 mm3) was completely inhibited concomitantly with an accumulation of the ODN throughout the tumor. These data show that the cRaf-AS is a highly efficacious antitumor agent, provided accessibility into the tumor tissue is warranted, and suggest that PS-AS-ODN treatment may be particularly useful in an adjuvant setting.  相似文献   
999.
Endogenous cysteine proteases were given much attention lately, as their role in a variety of pathophysiological disorders became evident. Amongst them cathepsins, which are thought to be implicated in mediation of osteoporosis, cancer progression, atherosclerosis, and many other conditions, are of considerable interest as drug targets. In the presented work, papain was chosen as a model cysteine protease and panning protocol was optimized for selection of papain-binding phage-displayed peptides from a commercially available combinatorial peptide library. Different selection strategies were applied in order to select high-affinity binders. Ultimately, five cyclic peptides (CNWAAGYNCGGGS-NH2, CWSMMGFQCGGGS-NH2, CWEWGGWHCGGSS-OH, CNWTLGGYKCGGGS-NH2 (all cyclized through formation of intramolecular disulphide bond), and GNWTLGGYKGG (cyclized head-to-tail)) were synthesized and tested for inhibitory activity towards papain and human cathepsins L, B, H, and K. The peptides possess inhibitory constants in the low micromolar to mid-nanomolar range and exhibit certain selectivity for different lysosomal cysteine proteases included in this study.  相似文献   
1000.
Four platinum(IV) complexes, trans,trans-dichlorobis(N,N-dimethylglycinato)platinum(IV), trans,trans-[Pt(dmgly)2Cl2] (1) and trans,trans-dibromobis(N,N-dimethylglycinato)platinum (IV), trans,trans-[Pt(dmgly)2Br2] (2), as well as, trans,trans-dichlorobis(N-methylglycinato)platinum(IV), trans,trans-[Pt(sar)2Cl2] (3) and trans,trans-dibromobis(N-methylglycinato)platinum(IV), trans,trans-[Pt(sar)2Br2] (4) (with configuration index for all complexes OC-6-14), were synthesized and characterized by elemental analysis, infrared and 1H NMR spectroscopy. In the aim to assess the selectivity in the antitumor action of these complexes, the antiproliferative action of these compounds was determined to human adenocarcinoma HeLa cells; to human myelogenous leukemia K562 cells and to normal immunocompetent cells; i.e., on human PBMC. The details of the crystal structure synthesized trans,trans-[Pt(sar)2Br2] complex were also reported here. In the crystal structure of trans,trans-[Pt(sar)2Br2], the Pt(IV) ion had a deformed octahedral coordination with both N-methylglycinates and bromides bonded trans to one another and with the N-Pt-Br bond angles of 84.1(4) and 95.9(4)°. The trans,trans-[Pt(sar)2Br2] complex molecules form 2D-layers with multiple N-H?O and C-H?O hydrogen bonds.  相似文献   
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号