全文获取类型
收费全文 | 738篇 |
免费 | 37篇 |
国内免费 | 3篇 |
专业分类
778篇 |
出版年
2024年 | 2篇 |
2023年 | 9篇 |
2022年 | 22篇 |
2021年 | 44篇 |
2020年 | 20篇 |
2019年 | 35篇 |
2018年 | 36篇 |
2017年 | 21篇 |
2016年 | 22篇 |
2015年 | 35篇 |
2014年 | 35篇 |
2013年 | 73篇 |
2012年 | 65篇 |
2011年 | 57篇 |
2010年 | 23篇 |
2009年 | 21篇 |
2008年 | 35篇 |
2007年 | 37篇 |
2006年 | 27篇 |
2005年 | 26篇 |
2004年 | 23篇 |
2003年 | 18篇 |
2002年 | 12篇 |
2001年 | 8篇 |
2000年 | 2篇 |
1999年 | 9篇 |
1998年 | 5篇 |
1997年 | 3篇 |
1996年 | 2篇 |
1995年 | 1篇 |
1994年 | 2篇 |
1993年 | 5篇 |
1992年 | 2篇 |
1991年 | 4篇 |
1990年 | 9篇 |
1989年 | 2篇 |
1988年 | 3篇 |
1987年 | 5篇 |
1986年 | 1篇 |
1985年 | 1篇 |
1984年 | 1篇 |
1982年 | 4篇 |
1981年 | 1篇 |
1980年 | 3篇 |
1977年 | 1篇 |
1976年 | 1篇 |
1975年 | 3篇 |
1974年 | 1篇 |
1973年 | 1篇 |
排序方式: 共有778条查询结果,搜索用时 15 毫秒
31.
Takhi M Singh G Murugan C Thaplyyal N Maitra S Bhaskarreddy KM Amarnath PV Mallik A Harisudan T Trivedi RK Sreenivas K Selvakumar N Iqbal J 《Bioorganic & medicinal chemistry letters》2008,18(18):5150-5155
Novel oxazolidinone antibacterials bearing a variety of 3-indolylglyoxamide substituents have been explored in an effort to improve the spectrum and potency of this class of agents. A subclass of this series was also made with the diversity at C-5 terminus. These derivatives have been screened against a panel of clinically relevant Gram-positive pathogens and fastidious Gram-negative organisms. Several analogs in this series were identified with in vitro activity superior to linezolid (MIC=0.25-2 microg/mL). Compounds 10a, 10c, 10e and 10f displayed activity against linezolid resistant Gram-positive organisms (MIC=2-4 microg/mL). Selected oxazolidinones were evaluated for in vivo efficacy against a mouse systemic infection model. 相似文献
32.
Abedi-Ardekani B Kamangar F Sotoudeh M Villar S Islami F Aghcheli K Nasrollahzadeh D Taghavi N Dawsey SM Abnet CC Hewitt SM Fahimi S Saidi F Brennan P Boffetta P Malekzadeh R Hainaut P 《PloS one》2011,6(12):e29488
Background
Golestan Province in northeastern Iran has one of the highest incidences of esophageal squamous cell carcinoma (ESCC) in the world with rates over 50 per 100,000 person-years in both sexes. We have analyzed TP53 mutation patterns in tumors from this high-risk geographic area in search of clues to the mutagenic processes involved in causing ESCC.Methodology/Principal Findings
Biopsies of 119 confirmed ESCC tumor tissue from subjects enrolled in a case-control study conducted in Golestan Province were analyzed by direct sequencing of TP53 exons 2 through 11. Immunohistochemical staining for p53 was carried out using two monoclonal antibodies, DO7 and 1801. A total of 120 TP53 mutations were detected in 107/119 cases (89.9%), including 11 patients with double or triple mutations. The mutation pattern was heterogeneous with infrequent mutations at common TP53 “hotspots” but frequent transversions potentially attributable to environmental carcinogens forming bulky DNA adducts, including 40% at bases known as site of mutagenesis by polycyclic aromatic hydrocarbons (PAHs). Mutations showed different patterns according to the reported temperature of tea consumption, but no variation was observed in relation to ethnicity, tobacco or opium use, and alcoholic beverage consumption or urban versus rural residence.Conclusion/Significance
ESCC tumors in people from Golestan Province show the highest rate of TP53 mutations ever reported in any cancer anywhere. The heterogeneous mutation pattern is highly suggestive of a causative role for multiple environmental carcinogens, including PAHs. The temperature and composition of tea may also influence mutagenesis. 相似文献33.
Das J Sitaram Kumar M Subrahmanyam D Sastry TV Prasad Narasimhulu C Laxman Rao CV Kannan M Roshaiah M Awasthi R Patil SN Sarnaik HM Rao Mamidi NV Selvakumar N Iqbal J 《Bioorganic & medicinal chemistry》2006,14(23):8032-8042
In an effort to discover potent antibacterials based on the entropically favored 'bioactive conformation' approach, a series of novel tricyclic molecules mimicking the conformationally constrained structure of Linezolid is reported. Based on the initial tricyclic molecule 1, the benzazepine derivative 2 was designed where the tricyclic structure had more flexibility around C-N bond compared to 1. While, the molecule 2 was less active, the molecule 3 showed promising antibacterial activity presumably after having obtained rigidity due to pyrrole ring. The syntheses, SAR studies, and evaluation of 3 as a lead compound are reported. 相似文献
34.
Naeem lqbal Muhammad Yasin Ashraf Farrukh Javed Muhammad Ashmf Sohail Hameed 《植物学报(英文版)》2006,48(5):558-562
In the present study, the relationship between the nutritional status of leaves and the development of symptoms of cotton leaf curl virus (CLCuV) in two cotton (Gossypium hirsutum L.) cuItlvars (I.e. CIM-240 and S-12) was Investigated. The incidence of disease attack was found to be 100% In the S-12 cuItlvar and 16% in the CIM-240 cuItivar. Geminivirus particles in infected leaves were confirmed by transmission electron microscope examination of highly specific geminivirus coat protein antlsera-treated cell sap. The CLCuV Impaired the accumulation of different nutrients in both cuItivars. A marked decrease in the accumulation of Ca^2+ and K^+ was observed in infected leaves. However, the disease had no effect on leaf concentrations of Na^+, N, and P. It was observed that the curling of leaf margins in CLCuV-Infected plants was associated with the leaf Ca^2+ content; leaf curling was severe in plants with a significant reduction In Ca^2+ content. Moreover, leaf K&+ content was found to be associated with resistance/susceptibility to CLCuV infection. 相似文献
35.
Jabbar A Rashid MH Javed MR Perveen R Malana MA 《Journal of industrial microbiology & biotechnology》2008,35(6):515-524
Gymnoascella citrina produced two isoforms of endoglucanases (CMCase-I and -capital I, Ukrainiancapital I, Ukrainian) under solid-state condition. Purified CMCase-I was novel because it was apparently holoenzyme in nature. The enzyme was monomeric as its native and subunit mass were almost the same, i.e., 43 and 42 kDa, respectively. Ea for carboxymethylcellulose (CMC) hydrolysis was 36.2 kJ mol(-1). The enzyme was stable over a pH range of 3.5-6.5, while temperature optimum was 55 degrees C. Vmax, Km and k (cat )for CMC hydrolysis were 39 U mg(-1) protein, 6.25 mg CMC mL(-1) and 27.5 s(-1), respectively. The pKa1 and pKa2 of ionizable groups of active site were 2.8 and 7.4, respectively. Thermodynamic parameters for CMC hydrolysis were as follows: DeltaH*=33.5 kJ mol(-1), DeltaG*=70.42 kJ mol(-1) and DeltaS*=-114.37 J mol(-1) K(-1). The removal of metals resulted into complete loss of enzymatic activity and was completely recovered in the presence of 1 mM Mn2+, whereas inhibition initiated at 5 mM. The other metals like Ca2+, Zn2+ and K1+ showed no inhibition up to 7 mM, Co2+ completely inhibited the activity, while Mg2+ could not recover the initial activity up to 7 mM. So we are reporting for the first time, kinetics and thermodynamics of CMCase-Iota from G. citrina. 相似文献
36.
37.
Chemical modification of lysine residues in glucose oxidase was carried out using citraconic anhydride. Modification brought about changes in the kinetic properties of the enzyme as evident by substantial lowering of V(max) and K(m). Enhancement of tryptophan fluorescence was observed with a dramatic change in its pH dependence due to modification. Near- and far-UV circular dichroism spectra of the native and modified forms suggested formation of molten globule-like structures, further supported by 8-anilino-1-naphthalenesulfonic acid fluorescence which indicated higher exposure of hydrophobic residues as a result of chemical modification. 相似文献
38.
Zonouzi R Ashtiani SK Hosseinkhani S Baharvand H 《Journal of biochemistry and molecular biology》2006,39(4):426-431
Embryonic stem cells (ESCs), representing a population of undifferentiated pluripotent cells with both self-renewal and multilineage differentiation characteristics, are capable of spontaneous differentiation into cardiomyocytes. The present study sought to define the kinetic characterization of lactate dehydrogenase (LDH) and creatine kinase (CK) of ESC- and neonatal-derived cardiomyocytes. Spontaneously differentiated cardiomyocytes from embryoid bodies (EBs) derived from mouse ESC line (Royan B1) and neonatal cardiomyocytes were dispersed in a buffer solution. Enzymes were extracted by sonication and centrifugation for kinetic evaluation of LDH and CK with spectrophotometric methods. While a comparison between the kinetic properties of the LDH and CK of both groups revealed not only different Michaelis constants and optimum temperatures for LDH but also different Michaelis constants and optimum pH for CK, the pH profile of LDH and optimum temperature of CK were similar. In defining some kinetic properties of cardiac metabolic enzymes of ESC-derived cardiomyocytes, our results are expected to further facilitate the use of ESCs as an experimental model. 相似文献
39.
Kaushalya C Amarasinghe Jason Li Sally M Hunter Georgina L Ryland Prue A Cowin Ian G Campbell Saman K Halgamuge 《BMC genomics》2014,15(1)
Background
Using whole exome sequencing to predict aberrations in tumours is a cost effective alternative to whole genome sequencing, however is predominantly used for variant detection and infrequently utilised for detection of somatic copy number variation.Results
We propose a new method to infer copy number and genotypes using whole exome data from paired tumour/normal samples. Our algorithm uses two Hidden Markov Models to predict copy number and genotypes and computationally resolves polyploidy/aneuploidy, normal cell contamination and signal baseline shift. Our method makes explicit detection on chromosome arm level events, which are commonly found in tumour samples. The methods are combined into a package named ADTEx (Aberration Detection in Tumour Exome). We applied our algorithm to a cohort of 17 in-house generated and 18 TCGA paired ovarian cancer/normal exomes and evaluated the performance by comparing against the copy number variations and genotypes predicted using Affymetrix SNP 6.0 data of the same samples. Further, we carried out a comparison study to show that ADTEx outperformed its competitors in terms of precision and F-measure.Conclusions
Our proposed method, ADTEx, uses both depth of coverage ratios and B allele frequencies calculated from whole exome sequencing data, to predict copy number variations along with their genotypes. ADTEx is implemented as a user friendly software package using Python and R statistical language. Source code and sample data are freely available under GNU license (GPLv3) at http://adtex.sourceforge.net/.Electronic supplementary material
The online version of this article (doi:10.1186/1471-2164-15-732) contains supplementary material, which is available to authorized users. 相似文献40.
Metal tolerance in tissue cultures of anthoxanthum odoratum 总被引:1,自引:0,他引:1
Javed A. Qureshi Hamish A. Collin Keith Hardwick David A. Thurman 《Plant cell reports》1981,1(2):80-82
Tissue cultures were initiated from one non-tolerant (S20) and two zinc and lead tolerant (T92 and T94) clones of Anthoxanthum odoratum. Growth of callus from the non-tolerant clone was reduced by the presence of zinc, lead, copper and nickel, whereas callus from the two tolerant clones showed no reduction of growth in the presence of zinc and lead but growth was reduced by copper and nickel. The specificity of metal tolerance shown by the parental material was maintained in the callus. Tolerant and non-tolerant callus accumulated similar amounts of zinc and lead. 相似文献