全文获取类型
收费全文 | 940篇 |
免费 | 20篇 |
专业分类
960篇 |
出版年
2024年 | 6篇 |
2023年 | 11篇 |
2022年 | 19篇 |
2021年 | 42篇 |
2020年 | 39篇 |
2019年 | 79篇 |
2018年 | 50篇 |
2017年 | 40篇 |
2016年 | 45篇 |
2015年 | 41篇 |
2014年 | 42篇 |
2013年 | 79篇 |
2012年 | 78篇 |
2011年 | 70篇 |
2010年 | 49篇 |
2009年 | 35篇 |
2008年 | 32篇 |
2007年 | 46篇 |
2006年 | 37篇 |
2005年 | 20篇 |
2004年 | 21篇 |
2003年 | 20篇 |
2002年 | 17篇 |
2001年 | 6篇 |
2000年 | 5篇 |
1999年 | 6篇 |
1998年 | 5篇 |
1997年 | 5篇 |
1996年 | 1篇 |
1995年 | 3篇 |
1993年 | 1篇 |
1991年 | 1篇 |
1990年 | 2篇 |
1989年 | 1篇 |
1988年 | 2篇 |
1987年 | 2篇 |
1986年 | 1篇 |
1985年 | 1篇 |
排序方式: 共有960条查询结果,搜索用时 128 毫秒
31.
32.
Mehri Abedi Reza Ahangari Cohan Fereidoun Mahboudi Mohammad Ali Faramarzi Ramin Fazel Narges Damavandi Mehdi Shafiee Ardestani Fatemeh Davami 《Journal of cellular physiology》2019,234(10):18206-18213
Antibody-drug conjugates are now of considerable interest and are recommended for the treatment of cancers. Linkers are having a crucial role in potency and efficacy of these drugs. Herein, for the first time, we have used a water-soluble poly-ethylene glycol based linker (succinimidyl-[(N-maleimido propionamido)-diethyleneglycol] [SM(PEG)2]) for lysine amide coupling of DM1 drug to trastuzumab considering evaluation of the effect of using a hydrophilic linker on physicochemical and biological properties of the resulting conjugate in comparison to the conjugate containing succinimidyl 4-(N-maleimidomethyl) cyclohexane-1-carboxylate (SMCC) linker, which has a relative hydrophobic nature. The physicochemical properties of synthesized conjugates were investigated in terms of drug to antibody ratio, size variants and free drug quantities. In vitro biological activity of trastuzumab-DM1 conjugates was assessed on breast cancer cell lines expressing different levels of HER2 using binding affinity, antiproliferative, apoptosis, and antibody-dependent cell-mediated cytotoxicity (ADCC) assays. Synthesized conjugate containing hydrophilic linker, showed higher drug to antibody ratio, no aggregated form and higher cellular toxicity in comparison to SMCC bearing conjugate. Binding affinity and ADCC potential of conjugates was not affected upon the usage of hydrophilic linker. In conclusion, application of SM(PEG)2 for coupling of DM1 to trastuzumab enhance desirable characteristics of the resulting conjugate. 相似文献
33.
Cysteinyl-leukotrienes and the liver 总被引:3,自引:0,他引:3
Leukotrienes are potent biological mediators implicated in an increasing number of disease processes. This review outlines the basic biology of leukotrienes and discusses recent developments in our understanding of the specific role of cysteinyl-leukotrienes (cLTs) in cholestasis, hepatic inflammation, portal hypertension, and the pathogenesis of the hepatorenal syndrome (HRS). 相似文献
34.
Nathanaelle Saclier;Louis Duchemin;Lara Konecny-Dupré;Philippe Grison;David Eme;Chloé Martin;Cécile Callou;Tristan Lefébure;Clémentine François;Colin Issartel;Julian J. Lewis;Fabio Stoch;Boris Sket;Sanja Gottstein;Teo Delić;Maja Zagmajster;Michal Grabowski;Dieter Weber;Ana Sofia P. S. Reboleira;Dmitry Palatov;Kaloust Paragamian;Lee R. F. D. Knight;Georges Michel;Francois Lefebvre;Mohammad-Javad Malek Hosseini;Ana I. Camacho;Begoña Gartzia De Bikuña;Amina Taleb;Nouria Belaidi;Raoul P. Tuekam Kayo;Diana Maria Paola Galassi;Oana Teodora Moldovan;Christophe J. Douady;Florian Malard; 《Molecular ecology resources》2024,24(1):e13882
Transition to novel environments, such as groundwater colonization by surface organisms, provides an excellent research ground to study phenotypic evolution. However, interspecific comparative studies on evolution to groundwater life are few because of the challenge in assembling large ecological and molecular resources for species-rich taxa comprised of surface and subterranean species. Here, we make available to the scientific community an operational set of working tools and resources for the Asellidae, a family of freshwater isopods containing hundreds of surface and subterranean species. First, we release the World Asellidae database (WAD) and its web application, a sustainable and FAIR solution to producing and sharing data and biological material. WAD provides access to thousands of species occurrences, specimens, DNA extracts and DNA sequences with rich metadata ensuring full scientific traceability. Second, we perform a large-scale dated phylogenetic reconstruction of Asellidae to support phylogenetic comparative analyses. Of 424 terminal branches, we identify 34 pairs of surface and subterranean species representing independent replicates of the transition from surface water to groundwater. Third, we exemplify the usefulness of WAD for documenting phenotypic shifts associated with colonization of subterranean habitats. We provide the first phylogenetically controlled evidence that body size of males decreases relative to that of females upon groundwater colonization, suggesting competition for rare receptive females selects for smaller, more agile males in groundwater. By making these tools and resources widely accessible, we open up new opportunities for exploring how phenotypic traits evolve in response to changes in selective pressures and trade-offs during groundwater colonization. 相似文献
35.
Mazhari-Tabrizi R Blank M Mumberg D Funk M Schwarz RT Eckert V 《Glycoconjugate journal》1999,16(11):673-679
Heterologous complementation in yeast has been a successful tool for cloning and characterisation of genes from various organisms. Therefore we constructed conditionally lethal Saccharomyces cerevisiae strains by replacing the endogenous promoter from the genes of interest (glycosyltransferases) by the stringently regulated GAL1-promoter, by a technique called chromosomal promoter replacement. Such yeast strains were constructed for the genes Alg 1, Alg7, Sec59, Wbp1 involved in N-Glycosylation, the genes Gpi2, Gpi3/Spt14, Gaal, Pis1, involved in GPI-anchor biosynthesis and Dpm involved in both pathways. All strains show the expected conditionally lethal phenotype on glucose-containing medium when expression of the respective gene is turned off. 相似文献
36.
Bovine serum albumin (BSA) has various applications in blood group serology and different research purposes. In this study purification of BSA has been compared with human serum albumin (HSA) using modified ethanol precipitation method based on the method of Cohn. The purification process was carried out under controlled conditions, particularly of ethanol concentration, pH, ionic strength and temperature. It was revealed that the produced BSA and HSA have purity more than 95%. It is obvious that HSA can be used, as a drug when the amount of its polymers is less than 5% whereas polymer generation is required in order to enhance the potentiating properties of BSA in agglutination of red cells. We propose here a simple and rapid two-step method for simultaneously purification and polymerization of BSA. By this method simply BSA with desired amount of polymers was obtained by 40% ethanol concentration. 相似文献
37.
Filip Vujovic Saba Rezaei-Lotfi Neil Hunter Ramin M Farahani 《Nucleic acids research》2021,49(18):10419
38.
Akram Yahyaabadi Falamarz Torkzadeh Dariush Rezaei Ochbelagh Seyed Mahdi Hosseini Pooya 《Luminescence》2018,33(5):891-896
LiF:Mg,Cu,Ag is a new dosimetry material that is similar to LiF:Mg,Cu,P in terms of dosimetric properties. The effect of the annealing temperature in the range of 200 to 350°C on the thermoluminescence (TL) sensitivity and the glow curve structure of this material at different concentrations of silver (Ag) was investigated. It has been demonstrated that the optimum values of the annealing temperature and the Ag concentration are 240°C and 0.1 mol% for better sensitivity, respectively. The TL intensity decreases at annealing temperatures lower than 240°C or higher than 240°C, reaching a minimum at 300°C and then again increases for various Ag concentrations. It was observed that the glow curve structure altered and the area under the low temperature peak as well as the area under the main dosimetric peak decreased with increasing annealing temperature. The position of the main dosimetric peak moved in the direction of higher temperatures, but at 320 and 350°C annealing temperatures, it shifted to lower temperatures. It was also observed that the TL sensitivity could partially be recovered by a combined annealing procedure. 相似文献
39.
Parviez Rana Hosseini Trevon Fuller Ryan Harrigan Delong Zhao Carmen Sofia Arriola Armandoe Gonzalez Matthew Joshua Miller Xiangming Xiao Tom B. Smith Jamie Holland Jones Peter Daszak 《PloS one》2013,8(12)
Highly pathogenic influenza A/H5N1 has persistently but sporadically caused human illness and death since 1997. Yet it is still unclear how this pathogen is able to persist globally. While wild birds seem to be a genetic reservoir for influenza A, they do not seem to be the main source of human illness. Here, we highlight the role that domestic poultry may play in maintaining A/H5N1 globally, using theoretical models of spatial population structure in poultry populations. We find that a metapopulation of moderately sized poultry flocks can sustain the pathogen in a finite poultry population for over two years. Our results suggest that it is possible that moderately intensive backyard farms could sustain the pathogen indefinitely in real systems. This fits a pattern that has been observed from many empirical systems. Rather than just employing standard culling procedures to control the disease, our model suggests ways that poultry production systems may be modified. 相似文献
40.
Posttranscriptional stimulation of endothelial cell matrix metalloproteinases 2 and 1 by endothelioma cells 总被引:7,自引:0,他引:7