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   1515篇
  免费   112篇
  2023年   3篇
  2022年   12篇
  2021年   34篇
  2020年   23篇
  2019年   26篇
  2018年   39篇
  2017年   33篇
  2016年   47篇
  2015年   81篇
  2014年   87篇
  2013年   132篇
  2012年   130篇
  2011年   115篇
  2010年   91篇
  2009年   70篇
  2008年   120篇
  2007年   84篇
  2006年   90篇
  2005年   84篇
  2004年   59篇
  2003年   67篇
  2002年   52篇
  2001年   9篇
  2000年   7篇
  1999年   12篇
  1998年   12篇
  1997年   11篇
  1996年   9篇
  1995年   9篇
  1994年   3篇
  1993年   6篇
  1992年   7篇
  1991年   8篇
  1990年   5篇
  1989年   3篇
  1988年   7篇
  1987年   2篇
  1986年   2篇
  1985年   6篇
  1984年   7篇
  1983年   4篇
  1982年   2篇
  1981年   6篇
  1980年   2篇
  1977年   1篇
  1976年   1篇
  1975年   1篇
  1974年   2篇
  1970年   1篇
  1965年   1篇
排序方式: 共有1627条查询结果,搜索用时 312 毫秒
991.
992.
Disentangling the demographic processes that determine the genetic structure of a given species is a fundamental question in conservation and management. In the present study, the population structure of the European eel was examined with a multidisciplinary approach combining the fields of molecular genetics and population dynamics modelling. First, we analyzed a total of 346 adult specimens of known age collected in three separate sample sites using a large panel of 22 EST-linked microsatellite loci. Second, we developed a European eel-specific model to unravel the demographic mechanisms that can produce the level of genetic differentiation estimated by molecular markers. This is the first study that reveals a pattern of genetic patchiness in maturing adults of the European eel. A highly significant genetic differentiation was observed among samples that did not follow an Isolation-by-Distance or Isolation-by-Time pattern. The observation of genetic patchiness in adults is likely to result from a limited parental contribution to each spawning event as suggested by our modelling approach. The value of genetic differentiation found is predicted by the model when reproduction occurs in a limited number of spawning events isolated from each other in time or space, with an average of 130-375 breeders in each spawning event. Unpredictability in spawning success may have important consequences for the life-history evolution of the European eel, including a bet-hedging strategy (distributing reproductive efforts over time) which could in turn guarantee successful reproduction of some adults.  相似文献   
993.
994.
Giardia intestinalis is the microaerophilic protozoon causing giardiasis, a common infectious intestinal disease. Giardia possesses an O(2) -scavenging activity likely essential for survival in the host. We report that Giardia trophozoites express the O(2) -detoxifying flavodiiron protein (FDP), detected by immunoblotting, and are able to reduce O(2) to H(2) O rapidly (~3 μM O(2) × min × 10(6) cells at 37 °C) and with high affinity (C(50) = 3.4 ± 0.7 μM O(2)). Following a short-term (minutes) exposure to H(2) O(2) ≥ 100 μM, the O(2) consumption by the parasites is irreversibly impaired, and the FDP undergoes a degradation, prevented by the proteasome-inhibitor MG132. Instead, H(2) O(2) does not cause degradation or inactivation of the isolated FDP. On the basis of the elevated susceptibility of Giardia to oxidative stress, we hypothesize that the parasite preferentially colonizes the small intestine since, compared with colon, it is characterized by a greater capacity for redox buffering and a lower propensity to oxidative stress.  相似文献   
995.
Abstract

The composition of the stigmatic exudate of Citrus limon (L.) Burm. - Biochemical analyses of the stigmatic exudate of Citrus limon (L.) Burm. have revealed the presence of lipids, polysaccharides, proteins, phenols, free aminoacids and alkaloids. The role of stigma secretion is discussed in relation to pollen activation and recognition and the pollen tube growth.  相似文献   
996.
Metal complexes of a sulfonamide possessing strong carbonic anhydrase (CA) inhibitory properties, 5-(2-chlorophenyl)-1, 3, 4-thiadiazole-2-sulfonamide (chlorazolamide) have been obtained from the sodium salt of the sulfonamide and the following metal ions: Mg(II), Zn(II), Mn(II), Cu(II), Co(II), Ni(II), Be(II), Cd(II), Pb(II), AI(III), Fe(III) and La(III). The original sulfonamide and its complexes were assayed for the in vitro inhibition of three CA isozymes, CA I, II, and IV, some of which play a critical role in ocular fluid secretion. All these compounds (the sulfonamide and its metal complexes) behaved as powerful inhibitors against the three investigated isozymes. The parent sulfonamide possessed an extremely weak topical pressure lowering effect when administered as a 1-2% suspension into the rabbit eye, but some of its metal complexes, such as the Mg(II), Zn(II), Mn(II) and Cu(II) derivatives, lower intraocular pressure (IOP) in experimental animals very well. Ex vivo data showed a 99.5-99.9% CA II inhibition in ocular fluids and tissues of rabbits treated with these agents, proving that the observed IOP lowering is due to CA inhibition. The influence of the different metal ions upon the efficiency of the obtained complexes as pressure lowering drugs are discussed, leading to the possibility of designing more selective; potent pharmacological agents from this class  相似文献   
997.
Milk xanthine oxidase (xanthine: oxygen oxidore-ductase; XO; EC 1.1.3.22) was found to catalyze the conversion of retinaldehyde to retinoic acid. The ability of XO to synthesize all trans-retinoic acid efficiently was assessed by its turnover number of 31.56 min?1, determined at pH 7.0 with 1nM XO and all trans-retinaldehyde varying between 0.05 to 2μM. The determination of both retinoid and purine content in milk was also considered in order to correlate their concentrations with kinetic parameters of retinaldehyde oxidase activity. The velocity of the reaction was dependent on the isomeric form of the substrate, the all trans- and 9-cis-forms being the preferred substrates rather than 13-cis-retinaldehyde. The enzyme was able to oxidize retinaldehyde in the presence of oxygen with NAD or without NAD addition. In this latter condition the catalytic efficiency of the enzyme was higher. The synthesis of retinoic acid was inhibited 87% and 54% by 4μM and 2μM allopurinol respectively and inhibited 48% by 10 μM xanthine in enzyme assays performed at 2μM all trans-retinaldehyde. The Ki value determined for xanthine as an inhibitor of retinaldehyde oxidase activity was 4 μM.  相似文献   
998.
Abstract

The hydrolytic activity of the 1,3,5-triaminocycloxexane derivatives TACH, TACI and TMCA complexed to Zn(II) and Cu(II) towards a model phosphoric ester and plasmid DNA has been evaluated by means of spectroscopic and gel-electrophoresis techniques. At conditions close to physiological, a prominent cleavage effect mediated by the nature of the ligand and metal ion was generally observed. TACI complexes are the most active in relaxing supercoiled DNA, the effect being explained by the affinity of the hydroxylated ligand for the nucleic acid. As indicated by the dependence of cleavage efficiency upon pH, Zn(II)-complexes act by a purely hydrolytic mechanism. In the case of Cu(II)-complexes, although hydrolysis should be prominent, involvement of an oxidative pathway cannot be completely ruled out.  相似文献   
999.
Development of extracellular plaques characteristic of Alzheimer's disease is related to aggregation of amyloid peptides. The Aβ-42 peptide is the most aggregation prone species, and some missense mutant forms increase this aggregation ability. Due to its poor solubility as monomer in aqueous solutions, Aβ-42 conformational transitions in water have been largely investigated by molecular dynamics. Here we report an all-atom molecular dynamics analysis of the Aβ-42 peptide in aqueous environment using as starting conformation a structure obtained in an isotropic, low-polarity medium, representing a plausible model for the membrane-bound species. While previous studies commonly show that Aβ-42 is largely unstructured in aqueous solution, here we report that this peptide can adopt partially folded structures. Importance of ionic strength has been also investigated, showing that at physiological ionic strength condition a loop stabilizing electrostatic interaction involving Lys28 builds up. In addition, besides stable α-helix structures, we observe the appearance of 310 helix, similar to what was reported experimentally for the Aβ-40 species. The effect of E22Q (Dutch) mutation in high ionic strength condition has been explored. We show that this mutation has a dramatic impact on the Aβ-42 structure. Instead of a partially folded, but extended, conformation obtained with the wild type, the E22Q assumes a two-helix collapsed one due to the clustering of hydrophobic residues.  相似文献   
1000.
Measurement of imatinib plasma concentration can be useful to evaluate patient adherence to daily oral therapy, potential drug–drug interaction, treatment efficacy, and severe drug-related adverse events. The aim of this study was to correlate the two different blood level test methods, HPLC–UV and LC–MS/MS. We analyzed 162 plasma samples from patients treated with imatinib. We estimated the correlation between the two analytical methods on total data set and on five sets of patients grouped into different categories based on the drug-dose therapy. Finally, imatinib quantification was correlated with genetic data on the molecular response in monitoring follow-up of CML patients.  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