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   4908篇
  免费   253篇
  国内免费   371篇
  2024年   12篇
  2023年   88篇
  2022年   155篇
  2021年   189篇
  2020年   150篇
  2019年   178篇
  2018年   187篇
  2017年   151篇
  2016年   143篇
  2015年   217篇
  2014年   352篇
  2013年   450篇
  2012年   266篇
  2011年   356篇
  2010年   231篇
  2009年   225篇
  2008年   247篇
  2007年   205篇
  2006年   188篇
  2005年   176篇
  2004年   159篇
  2003年   126篇
  2002年   118篇
  2001年   77篇
  2000年   57篇
  1999年   70篇
  1998年   62篇
  1997年   53篇
  1996年   67篇
  1995年   52篇
  1994年   41篇
  1993年   40篇
  1992年   46篇
  1991年   33篇
  1990年   31篇
  1989年   15篇
  1988年   24篇
  1987年   28篇
  1986年   27篇
  1985年   32篇
  1984年   54篇
  1983年   50篇
  1982年   39篇
  1981年   18篇
  1980年   14篇
  1979年   12篇
  1978年   4篇
  1977年   7篇
  1976年   4篇
  1974年   3篇
排序方式: 共有5532条查询结果,搜索用时 15 毫秒
51.
紫竹梅雄蕊毛细胞发育过程中胞间连丝超微结构的变化   总被引:6,自引:0,他引:6  
紫竹梅(Setcreasea purpurea)雄蕊毛细胞间的胞间连丝随着细胞的生长、发育、衰老而呈现动态变化的过程.花蕾和开放花的雄蕊毛细胞间的胞间连丝,具备胞间连丝的一般结构,直径约50 nm .衰老花雄蕊毛细胞间的胞间连丝拓宽,内部结构逐步降解、撤离,呈开放式通道,直径约100 nm . 在胞间连丝的动态开放过程中,细胞内的细胞器也发生相应变化. 对胞间连丝形成开放性通道及其机理进行了讨论  相似文献   
52.
    
Rat kidney-glutamylcysteine synthetase (GCS) was inactivated by reaction with trinitrobenzene sulfonate (TNBS), and the reaction followed pseudo-first-order kinetics. Inactivation kinetics revealed that only one of the amino acid residues modified by TNBS was essential for-GCS activity. The addition of 10 mM Mg2+ to the TNBS inactivation reaction resulted in a 16-fold increase in the rate of inactivation. Chromatographic analysis on the tryptic hydrolyzates of trinitrophenylated (TNP) derivatives showed that Lys-38 in theGCS heavy subunit was significantly modified in the presence of Mg2+. In contrast to small changes in the catalytic properties observed by mutation of Lys-38 to Arg, the mutants K38N and K38E had a marked decrease in enzymatic activity and about twofold increase inK m for glutamate. These results suggest that the positively charged Lys-38 may sbe involved in the binding of glutamate toGCS.  相似文献   
53.
Several peptide antibiotics have been described as potent inhibitors of bacterial growth. With respect to their biosynthesis, they can be devided into two classes: (i) those that are synthesized by a non-ribosomal mechanism and (ii) those that are ribosomally synthesized. Subtilin and nisin belong to the ribosomally synthesized peptide antibiotics. They contain the rare amino acids dehydroalanine, dehydrobutyrine, meso-lanthionine, and 3-methyl-lanthionine. They are derived from prepeptides which are post-translationally modiffied and have been termed lantibiotics because of their characteristic lanthionine bridges (Schnell et al. 1988). Nisin is the most prominent lantibiotic and is used as a food preservative due to its high potency against certain gram-positive bacteria (Mattick & Hirsch 1944, 1947; Rayman & Hurst 1984). It is produced by Lactococcus lactis strains belonging to serological group N. The potent bactericidal activities of nisin and other lantibiotics are based on depolarization of energized bacterial cytoplasmic membranes. Breakdown of the membrane potential is initiated by the formation of pores through which molecules of low molecular weight are released. A trans-negative membrane potential of 50 to 100 mV is necessary for pore formation by nisin (Ruhr & Sahl 1985; Sahl et al. 1987). Nisin occurs as a partially amphiphilic molecule (Van de Ven et al. 1991). Apart from the detergent-like effect of nisin on cytoplasmic membranes, an inhibition of murein synthesis has also been discussed as the primary effect (Reisinger et al. 1980). In several countries nisin is used to prevent the growth of clostridia in cheese and canned food. The nisin peptide structure was first described by Gross & Morall (1971), and its structural gene was isolated in 1988 (Buchman et al. 1988; Kaletta & Entian 1989). Nisin has two natural variants, nisin A and nisin Z, which differ in a single amino acid residue at position 27 (histidin in nisin A is replaced by asparagin in nisin Z (Mulders et al. 1991; De Vos et al. 1993). Subtilin is produced by Bacillus subtilis ATCC 6633. Its chemical structure was first unravelled by Gross & Kiltz (1973) and its structural gene was isolated in 1988 (Banerjee & Hansen 1988). Subtilin shares strong similarities to nisin with an identical organization of the lanthionine ring structures (Fig. 1), and both lantibiotics possess similar antibiotic activities. Due to its easy genetic analysis B. subtilis became a very suitable model organism for the identification and characterization of genes and proteins involved in lantibiotic biosynthesis. The pathway by which nisin is produced is very similar to that of subtilin, and the proteins involved share significant homologies over the entire proteins (for review see also De Vos et al. 1995b). The respective genes have been identified adjacent to the structural genes, and are organized in operon-like structures (Fig. 2). These genes are responsible for post-translational modification, transport of the modified prepeptide, proteolytic cleavage, and immunity which prevents toxic effects on the producing bacterium. In addition to this, biosynthesis of subtilin and nisin is strongly regulated by a two-component regulatory system which consists of a histidin kinase and a response regulator protein.  相似文献   
54.
Criteria for the evaluation of new drugs to treat obesity are important as guides for designing clinical trials to test these agents. These criteria must be developed in relation to the realities of obesity, which is a chronic disease associated with morbidity and mortality that is increased by visceral fat deposits. The observation that patients regain weight after stopping drug treatment for obesity argues for the proposition that drugs work only when taken and NOT that the drugs are ineffective. The analogy between the development of treatments for obesity to those for the treatment of hypertension is used to highlight potential areas for new developments. Several features of an ideal drug for the treatment of obesity are suggested. Criteria for evaluating new drugs include both primary and secondary endpoints. The primary endpoint for an anti-obesity drug should be weight loss, possibly by category of success. Losses of total body fat or visceral fat might be alternative primary endpoints. Secondary endpoints include reduction in risk factors for associated diseases and improvement in the quality of life. In trials where vigorous placebo designs including highly aggressive behavior modification or very-low-calorie diets were used, it may be difficult or impossible to detect a response to a drug.  相似文献   
55.
A number of different methods, involving direct DNA delivery are now available for plant transformation. Here we review the most recently developed technique which involves the mixing of silicon carbide whiskers with plant cells and plasmid DNA. Fertile transgenic plants have now been produced using whisker-mediated transformation, and this method can now be considered as a simple, inexpensive alternative for plant transformation. A brief review on transformation of animal cells andChlamydomonas using whiskers technology is also included.  相似文献   
56.
Poly(acrylonitrile-co-vinyl chloride) (PAN/VC) anisotropic membranes were chemically modified with poly(ethylene oxide) (PEO) (5000 and 20,000 g/mol) by one of two aqueous reactions: (a) acid hydrolysis of the nitrile group to a carboxylic acid with which amine-terminated PEO (PEO-NH(2)) reacted or (b) base reduction of the nitrile group to an amine with which PEO-succinimide (PEO-SC) reacted. Approximately 1.3% of the bulk material was modified with PEO-NH(2) whereas 1.8 to 3.5% was modified with PEO-SC as determined by proton nuclear magnetic resonance ((1)H NMR) and attenuated total reflectance Fourier transform infrared (ATR FTIR) spectra. Approximately 50 to 75% less bovine serum albumin (BSA) adsorbed to PEO-grafted single skin fibers than to unmodified PAN/VC. Transport properties of modified and unmodified fibers were compared by passive diffusion, convective nominal molecular weight cutoff, and hydraulic permeability. Neither hydraulic permeability nor nominal molecular weight cutoff of BSA changed appreciably after surface modification with PEO indicating that pore structure was not adversely affected by the chemistry involved in grafting poly(ethylene oxide). However, in the absence of any membrane conditioning, the apparent diffusion of alpha-chymotrypsinogen (24,000 g/mol) was enhanced in PEO-grafted PAN/VC fibers possibly as a result of reduced sorption of the permeating protein. In vivo biocompatibility in the brain tissue of rats was judged by histological assessment of the host's cellular response to fibers implanted for 30 days; biocompatibility of both PAN/VC and PAN/VC-g-PEO was satisfactory but improved slightly with PEO grafting. (c) 1994 John Wiley & Sons, Inc.  相似文献   
57.
Efficient production of ATP and NADPH by the light reactions of oxygen-evolving photosynthesis demands continuous adjustment of transfer of absorbed light energy from antenna complexes to Photosystem I (PS I) and II (PS II) reaction center complexes in response to changes in light quality. Treatment of intact cyanobacterial cells with N-ethylmaleimide appears to disrupt energy transfer from phycobilisomes to Photosystem I (PS I). Energy transfer from phycobilisomes to Photosystem II (PS II) is unperturbed. Spectroscopic analysis indicates that the individual complexes (phycobilisomes, PS II, PS I) remain functionally intact under these conditions. The results are consistent with the presence of connections between phycobiliproteins and both PS II and PS I, but they do not support the existence of direct contacts between the two photosystems.Abbreviations Chl chlorophyll - EPR electron paramagnetic resonance - NEM N-ethylmaleimide - PBS phycobilisome - PS photosystem  相似文献   
58.
59.
Two overlapping rat cDNAs, covering a continuous region of 1107 base pairs, have been isolated and sequenced. The clones contain identical open reading frames, encoding a 136 amino acid long polypeptide which exhibits 100% identity to other mammalian H3.3 histone variants. We show that the inserts derive, in particular, from the H3.3B gene. We used these inserts and an insert from an H1° encoding clone, previously described (6), as probes to study the accumulation of mRNAs encoding the corresponding histone replacement variants (namely, H1° and H3.3) during rat brain development. We found that the concentration of both H1° and H3.3B mRNAs decreases from the embryonal day 18 (E18) to the postnatal day 10 (P10), with inverse correlation to protein accumulation.This paper is dedicated to our friend Paolo Carbone who devoted his life to research and teaching in Genetics. We will always remember him for scientific honesty and for his unique qualities of humanity.  相似文献   
60.
Summary The interaction ofActinia equina equinatoxin II (EqT-II) with human red blood cells (HRBC) and with model lipid membranes was studied. It was found that HRBC hemolysis by EqT-II is the result of a colloid-osmotic shock caused by the opening of toxin-induced ionic pores. In fact, hemolysis can be prevented by osmotic protectants of adequate size. The functional radius of the lesion was estimated to be about 1.1 nm. EqT-II increased also the permeability of calcein-loaded lipid vesicles comprised of different phospholipids. The rate of permeabilization rised when sphingomyelin was introduced into the vesicles, but it was also a function of the pH of the medium, optimum activity being between pH 8 and 9; at pH 10 the toxin became markedly less potent. From the dose-dependence of the permeabilization it was inferred that EqT-II increases membrane permeability by forming oligomeric channels comprising several copies of the cytolysin monomer. The existence of such oligomers was directly demonstrated by chemical cross-linking. Addition of EqT-II to one side of a planar lipid membrane (PLM) increases the conductivity of the film in discrete steps of defined amplitude indicating the formation of cation-selective channels. The conductance of the channel is consistent with the estimated size of the lesion formed in HRBC. High pH and sphingomyelin promoted the interaction even in this system. Chemical modification of lysine residues or carboxyl groups of this protein changed the conductance, the ion selectivity and the current-voltage characteristic of the pore, suggesting that both these groups were present in its lumen.  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