全文获取类型
收费全文 | 1291篇 |
免费 | 50篇 |
国内免费 | 2篇 |
专业分类
1343篇 |
出版年
2023年 | 18篇 |
2022年 | 45篇 |
2021年 | 79篇 |
2020年 | 45篇 |
2019年 | 33篇 |
2018年 | 70篇 |
2017年 | 45篇 |
2016年 | 56篇 |
2015年 | 68篇 |
2014年 | 99篇 |
2013年 | 107篇 |
2012年 | 121篇 |
2011年 | 69篇 |
2010年 | 59篇 |
2009年 | 51篇 |
2008年 | 45篇 |
2007年 | 30篇 |
2006年 | 34篇 |
2005年 | 22篇 |
2004年 | 27篇 |
2003年 | 18篇 |
2002年 | 11篇 |
2001年 | 15篇 |
2000年 | 7篇 |
1999年 | 12篇 |
1998年 | 9篇 |
1997年 | 5篇 |
1996年 | 4篇 |
1993年 | 3篇 |
1992年 | 8篇 |
1991年 | 9篇 |
1990年 | 9篇 |
1989年 | 12篇 |
1988年 | 12篇 |
1987年 | 7篇 |
1986年 | 4篇 |
1985年 | 6篇 |
1984年 | 7篇 |
1983年 | 3篇 |
1982年 | 8篇 |
1981年 | 4篇 |
1980年 | 3篇 |
1975年 | 7篇 |
1974年 | 5篇 |
1973年 | 2篇 |
1972年 | 4篇 |
1971年 | 3篇 |
1970年 | 3篇 |
1969年 | 3篇 |
1966年 | 3篇 |
排序方式: 共有1343条查询结果,搜索用时 0 毫秒
1.
Abhishek Chatterjee Celia Caballero-Franco Dannika Bakker Stephanie Totten Armando Jardim 《The Journal of biological chemistry》2015,290(42):25579-25594
Enterohemorrhagic Escherichia coli is a causative agent of gastrointestinal and diarrheal diseases. Pathogenesis associated with enterohemorrhagic E. coli involves direct delivery of virulence factors from the bacteria into epithelial cell cytosol via a syringe-like organelle known as the type III secretion system. The type III secretion system protein EspD is a critical factor required for formation of a translocation pore on the host cell membrane. Here, we show that recombinant EspD spontaneously integrates into large unilamellar vesicle (LUV) lipid bilayers; however, pore formation required incorporation of anionic phospholipids such as phosphatidylserine and an acidic pH. Leakage assays performed with fluorescent dextrans confirmed that EspD formed a structure with an inner diameter of ∼2.5 nm. Protease mapping indicated that the two transmembrane helical hairpin of EspD penetrated the lipid layer positioning the N- and C-terminal domains on the extralumenal surface of LUVs. Finally, a combination of glutaraldehyde cross-linking and rate zonal centrifugation suggested that EspD in LUV membranes forms an ∼280–320-kDa oligomeric structure consisting of ∼6–7 subunits. 相似文献
2.
R C Kolbeck B A Chaudhary W A Speir 《Canadian journal of physiology and pharmacology》1989,67(11):1442-1447
The influence of hydrocortisone (11 beta, 17 alpha, 21-trihydroxy-pregn-4-ene-3,20-dione) or of methylprednisolone (6 alpha-methyl-11 beta, 17 alpha-21-trihydroxy-1,4-pregnadiene-3,20-dione) on the response of airway smooth muscle to a variety of beta-adrenergic bronchodilators was evaluated using incubated guinea pig tracheal rings, preconstricted with histamine. The adrenergic agonists chosen for this study included the nonselective beta 1- and beta 2-catecholamine, isoproterenol, the selective beta 2-catecholamine, rimiterol, and the selective beta 2-resorcinols, fenoterol and terbutaline. When the incubated rings were pretreated with 10-50 micrograms/mL of the steroids, there was a significant enhancement in smooth muscle sensitivity and reactivity to rimiterol and isoproterenol. Tracheal response to fenoterol or terbutaline, on the other hand, was not altered by the glucocorticoids. When used alone, neither steroid exerted an inotropic influence on the tracheal smooth muscle. The results of our study indicate that glucocorticoid enhancement of adrenergic bronchodilators is selective for catecholamines, and not for resorcinols. 相似文献
3.
Summary The extent of filter paper degradation by extracellular preparations fromT. reesei and its mutants with a decreasing level of -glucosidase and an increasing level of endoglucanase has been determined. The ability to degrade cellulose is restricted by the level of endoglucanase and not by -glucosidase. 相似文献
4.
The submicrosomal distribution of dolichyl phosphate and dolichyl phosphate phosphatase in rat liver 总被引:2,自引:0,他引:2
Rat liver microsomes were isolated and fractionated into Golgi, smooth endoplasmic reticulum (SER), and rough endoplasmic reticulum (RER), and the purity of these preparations was determined. The dolichyl phosphate (Dol-P) content of whole microsomes and of each of the submicrosomal fractions was estimated using high pressure liquid chromatography. Dol-P accounts for 4 and 40% of the sum of the alcohol, the fatty acyl esters of dolichol, and monophosphate forms present in whole liver and in purified microsomes, respectively. Concentrations equal to 58, 77, and 108 ng of Dol-P/mg of protein were found in Golgi, SER, and RER, respectively. These values represent 3, 36, and 54% of the sum of the alcohol, the fatty acyl esters of dolichol, and monophosphate forms present in each of these same fractions, respectively. Increases in the Dol-P content of rat liver were observed as early as 12 h after turpentine-induced inflammation and increased 2-fold over 36 h. In this system, Dol-P accounts for no more than 50% of the sum of all phosphorylated and pyrophosphorylated dolichol intermediates present. The specific activity for dolichyl phosphate phosphatase was highest by more than a factor of 2 in Golgi membrane. Specific activities obtained for SER and RER were 42 and 11% of those present in Golgi. The major requirement for Dol-P is thought to be for the saccharide and oligosaccharide transferase reactions which are presumed to take place in RER. The discovery of significant quantities of Dol-P in Golgi and SER is consistent with a possible role of Dol-P in the transport of sugars required for glycoprotein synthesis and processing from a cytosolic to luminal orientation. 相似文献
5.
B. D. Chaudhary R. K. Singh S. N. Kakar 《TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik》1974,45(5):192-196
Summary Four exotic and four indigenous strains of barley were used for making diallel crosses. The sets of parents and crosses making full, half and quarter diallel were analysed in a randomized block design for plant height, number of effective tillers, ear length, grain yield per plant, 100 grain weight and number of grains per ear.The three alternatives of diallel were similar with respect to the estimates of degree of dominance, general combining ability and specific combining ability, indicating that all these three methods of diallel were equally efficient. However, as the number of entries are minimum in quarter diallel, it would be economical in terms of cost, time and labour to estimate genetic parameters by this method. Average degree of dominance was found in the range of overdominance. The ranking of parents on the basis of their array mean was similar to the ranking based on gca effects. Similarly, the ranking of crosses on the basis of per se performance was similar to the ranking based on sca effects. This suggests that the selection of best general combiner or best cross combinations may be easier and more effective through array mean for per se performance rather than through high gca and sea effects, respectively. From among 56 crosses, IB-226 X X C-164 was the one which showed superiority for maximum number of characters followed by AB-12/59 X PTS-57. High sea effect for plant height, ear length, grain yield, 100 grain weight and number of grains per ear was the result of cross between parents having high X low general combining ability, indicating additive X dominance type of gene interaction. For number of effective tillers, high sca was produced by low x low general combiners, indicating dominance x dominance gene interaction.Part of a Ph. D. thesis submitted by senior author to Haryana Agricultural University, Hissar. 相似文献
6.
Proteases from human immunodeficiency virus and avian myeloblastosis virus show distinct specificities in hydrolysis of multidomain protein substrates. 下载免费PDF全文
A G Tomasselli J O Hui T K Sawyer D J Staples C A Bannow I M Reardon V K Chaudhary C M Fryling I Pastan D J Fitzgerald et al. 《Journal of virology》1990,64(7):3157-3161
The virally encoded proteases from human immunodeficiency virus (HIV) and avian myeloblastosis virus (AMV) have been compared relative to their ability to hydrolyze a variant of the three-domain Pseudomonas exotoxin, PE66. This exotoxin derivative, missing domain I and referred to as LysPE40, is made up of a 13-kilodalton NH2-terminal translocation domain II connected by a segment of 40 amino acids to enzyme domain III of the toxin, a 23-kilodalton ADP-ribosyltransferase. HIV protease hydrolyzes two peptide bonds in LysPE40, a Leu-Leu bond in the interdomain region and a Leu-Ala bond in a nonstructured region three residues in from the NH2-terminus. Neither of these sites is cleaved by the AMV enzyme; hydrolysis occurs, instead, at an Asp-Val bond in another part of the interdomain segment and at a Leu-Thr bond in the NH2-terminal region of domain II. Synthetic peptides corresponding to these cleavage sites are hydrolyzed by the individual proteases with the same specificity displayed toward the protein substrate. Peptide substrates for one protease are neither substrates nor competitive inhibitors for the other. A potent inhibitor of HIV type 1 protease was more than 3 orders of magnitude less active toward the AMV enzyme. These results suggest that although the crystallographic models of Rous sarcoma virus protease (an enzyme nearly identical to the AMV enzyme) and HIV type 1 protease show a high degree of similarity, there exist structural differences between these retroviral proteases that are clearly reflected by their kinetic properties. 相似文献
7.
Domain II mutants of Pseudomonas exotoxin deficient in translocation 总被引:16,自引:0,他引:16
Y Jinno M Ogata V K Chaudhary M C Willingham S Adhya D FitzGerald I Pastan 《The Journal of biological chemistry》1989,264(27):15953-15959
Pseudomonas exotoxin (PE) kills mammalian cells in a complex process that involves cell surface binding, internalization by endocytosis, translocation to the cytosol, and ADP-ribosylation of elongation factor 2. PE is a three-domain protein in which domain I binds to the cell surface, domain II promotes translocation into the cytosol, and domain III carries out ADP-ribosylation. To determine how translocation occurs, we have mutated all the arginine residues in domain II and found that mutations at positions 276 and 279 greatly diminished the cytotoxicity of PE and mutations 330 and 337 substantially reduced cytotoxicity. Biochemical studies indicate that after internalization into an endocytic compartment, the PE molecule undergoes a specific and saturable intracellular interaction, and this interaction is deficient in an Arg276----Gly mutant. Our data suggest that the translocation process of PE involves a specific interaction of Arg276 (and possibly Arg279, Arg330, and Arg337) with components of an intracellular compartment. 相似文献
8.
Characterization of human autoantibodies specific for lamin A 总被引:2,自引:0,他引:2
J C Courvalin N Chaudhary F Danon J C Brouet K Lassoued 《Biology of the cell / under the auspices of the European Cell Biology Organization》1990,69(2):93-97
We have characterized human autoimmune polyclonal antibodies reactive with lamin A, a 74 kDa peripheral protein of the nuclear envelope. Unlike other known antibodies to lamin A, the antibodies described here do not crossreact with the structurally related lamin C. These antibodies feature only chi light chains suggesting that their specificity is restricted to a limited number of epitopes. Based on the known amino acid sequence of human lamins A and C, the epitope(s) are most likely located in the 80 amino acid carboxyl tail of mature lamin A. 相似文献
9.
Sukriti Sacher Abhishek Mukherjee Arjun Ray 《Biological reviews of the Cambridge Philosophical Society》2023,98(4):1160-1183
Atherosclerosis is a major contributor to the onset and progression of cardiovascular disease (CVD). Cholesterol-loaded foam cells play a pivotal role in forming atherosclerotic plaques. Induction of cholesterol efflux from these cells may be a promising approach in treating CVD. The reverse cholesterol transport (RCT) pathway delivers cholesteryl ester (CE) packaged in high-density lipoproteins (HDL) from non-hepatic cells to the liver, thereby minimising cholesterol load of peripheral cells. RCT takes place via a well-organised interplay amongst apolipoprotein A1 (ApoA1), lecithin cholesterol acyltransferase (LCAT), ATP binding cassette transporter A1 (ABCA1), scavenger receptor-B1 (SR-B1), and the amount of free cholesterol. Unfortunately, modulation of RCT for treating atherosclerosis has failed in clinical trials owing to our lack of understanding of the relationship between HDL function and RCT. The fate of non-hepatic CEs in HDL is dependent on their access to proteins involved in remodelling and can be regulated at the structural level. An inadequate understanding of this inhibits the design of rational strategies for therapeutic interventions. Herein we extensively review the structure–function relationships that are essential for RCT. We also focus on genetic mutations that disturb the structural stability of proteins involved in RCT, rendering them partially or completely non-functional. Further studies are necessary for understanding the structural aspects of RCT pathway completely, and this review highlights alternative theories and unanswered questions. 相似文献
10.
Mohd Imran Shahzad Ahmed Ahmad Zuhairi Abdullah Jabir Hakami Anis Ahmad Chaudhary Hassan Ahmad Rudayni Salah-Ud-Din Khan Afzal Khan Nosiba Suliman Basher 《Luminescence》2023,38(7):1064-1086
The penicillin derivative amoxicillin (AMX) plays an important role in treating various types of infections caused by bacteria. However, excessive use of AMX may have negative health effects. Therefore, it is of utmost importance to detect and quantify the AMX in pharmaceutical drugs, biological fluids, and environmental samples with high sensitivity. Therefore, this review article provides valuable and up-to-date information on nanostructured material-based optical and electrochemical sensors to detect AMX in various biological and chemical samples. The role of using different nanostructured materials on the performance of important optical sensors such as colorimetric sensors, fluorescence sensors, surface-enhanced Raman scattering sensors, chemiluminescence/electroluminescence sensors, optical immunosensors, optical fibre-based sensors, and several important electrochemical sensors based on different electrode types have been discussed. Moreover, nanocomposites, polymer, and MXenes-based electrochemical sensors have also been discussed, in which such materials are being used to further enhance the sensitivity of these sensors. Furthermore, nanocomposite-based photo-electrochemical sensors and the market availability of biosensors including AMX have also been discussed briefly. Finally, the conclusion, challenges, and future perspectives of the above-mentioned sensing techniques for AMX detection are presented. 相似文献