全文获取类型
收费全文 | 616篇 |
免费 | 30篇 |
国内免费 | 4篇 |
专业分类
650篇 |
出版年
2024年 | 1篇 |
2023年 | 20篇 |
2022年 | 33篇 |
2021年 | 45篇 |
2020年 | 28篇 |
2019年 | 37篇 |
2018年 | 37篇 |
2017年 | 19篇 |
2016年 | 32篇 |
2015年 | 30篇 |
2014年 | 38篇 |
2013年 | 64篇 |
2012年 | 46篇 |
2011年 | 40篇 |
2010年 | 28篇 |
2009年 | 10篇 |
2008年 | 20篇 |
2007年 | 16篇 |
2006年 | 16篇 |
2005年 | 9篇 |
2004年 | 13篇 |
2003年 | 10篇 |
2002年 | 12篇 |
2001年 | 8篇 |
2000年 | 5篇 |
1999年 | 8篇 |
1998年 | 2篇 |
1997年 | 4篇 |
1996年 | 2篇 |
1995年 | 1篇 |
1994年 | 3篇 |
1993年 | 2篇 |
1992年 | 5篇 |
1991年 | 1篇 |
1985年 | 1篇 |
1984年 | 1篇 |
1976年 | 1篇 |
1973年 | 1篇 |
1872年 | 1篇 |
排序方式: 共有650条查询结果,搜索用时 15 毫秒
1.
N. Rehman A. R. Collins T. K. Suh R. W. Wright 《Molecular reproduction and development》1994,38(3):251-255
Development of 8-cell bovine embryos derived from in vitro matured/in vitro fertilized (IVM/IVF) oocytes was evaluated in two simple, serum-free media (CZB and SOM) with buffalo rat liver cells co-culture (BRLC) or after conditioning compared to a commonly used, serum-supplemented complex medium TCM-199. In a 3 x 4 factorial design, 578 eight-cell embryos were randomly assigned to 12 treatment groups. The factors were: first, type of culture medium (M199/FBS, CZBg and SOM), and second, the use of BRLC (as co-culture or to condition media for 24 hr and 48 hr) and unconditioned media. Development to morula was not affected by the type of medium, but co-culture and 48 hr conditioning within media type resulted in better development when compared to the 24-hr conditioned or unconditioned groups. Blastocyst development in SOM (38.9%) was different (P < 0.05) than in CZBg (46.6%) and M199/FBS (48.7%) and was lowest in the unconditioned group (27.8%) followed by 24 hr conditioned (33.3%), 48 hr (56.3%), and co-culture (59.6%). No blastocyst expansion was observed with unconditioned media and 24 hr conditioned SOM. Significant differences (P < 0.05) were found among all treatment groups except the co-culture and 48-hr conditioned groups. Hatching occurred only with co-culture and 48-hr conditioned groups of M199/FBS and CZBg media. These data show that CZB with glucose conditioned by BRLC monolayers for 48 hr can support the development of IVM/IVF produced bovine embryos to blastocyst compared to culture in TCM-199 with serum. © 1994 Wiley-Liss, Inc. 相似文献
2.
Dhurgham Al-Fahad Firas Alyaseen Ahmed Al-Amery Gagandeep Singh Mote Srinath Hafiz Muzzammel Rehman Yahya Abbas 《Reports of Biochemistry & Molecular Biology》2022,11(2):262
Background:The assembly and disassembly of the focal adhesions (FA) components occurs throughout life cycle of adhesion, with conservation of balance between removal and recruitment rate during temporal stages. Previous studies have demonstrated that phosphotidyilinositols play a role in regulating FA turnover. However, a little attention has been given to quantify the dynamics changes of Phosphatidylinositol 3,4,5-trisphosphate (PtdIns (3,4,5) P3) within and during fast and slow turnover rates of FA.Methods:In this study, we developed a protein purification MDA-MB-231 breast cancer cell line was used as a model in this study due to high metastatic and motile. These cells were co-transfected with GFP- paxillin/vinculin, as FA marker, and the GFP/mCherry-Btk-PH, as a biosensor to visualize PtdIns (3,4,5) P3. Confocal time-lapse images were used to monitor changes or differences in the local generation of PtdIns (3,4,5) P3 within and during assembly and disassembly of FA. Following transfection, immunostaining was used to examine the spatial co-localization between FA and PtdIns (3,4,5) P3.Results:Our data demonstrated that PtdIns (3,4,5) P3 co-localized with FAs and increase during assembly and decline during disassembly of FA which exhibits slow turnover rates and was in a constant level during assembly and disassembly of FA that displays fast turnover rates.DiscussionOur result suggested that the dynamic changes of PtdIns (3,4,5) P3, it may depend on components undergo turnover, such that early, nascent FA displays fast turnover rates and mature FA exhibits slow turnover rates. Thus, the local enrichment of PtdIns (3,4,5) P3 enhances FA assembly and disassembly activation.Key Words: Cancer cell migration, Focal adhesion turnover, MDA-MB-231 cell line, PtdIns (3,4,5) P3 相似文献
3.
Syed Mohsin Bukhari Huda Ahmed Alghamdi Khalil Ur Rehman Shahla Andleeb Shahbaz Ahmad Nimra Khalid 《Saudi Journal of Biological Sciences》2022,29(3):1781-1788
Pheasant reintroduction and conservation efforts have been in place in Pakistan since the 1980 s, yet there is still a scarcity of data on pheasant microbiome and zoonosis. Instead of growing vast numbers of bacteria in the laboratory, to investigate the fecal microbiome, pheasants (green and ring neck pheasant) were analyzed using 16S rRNA metagenomics and using IonS5TMXL sequencing from two flocks more than 10 birds. Operational taxonomic unit (OTU) cluster analysis and phylogenetic tree analysis was performed using Mothur software against the SSUrRNA database of SILVA and the MUSCLE (Version 3.8.31) software. Results of the analysis showed that firmicutes were the most abundant phylum among the top ten phyla, in both pheasant species, followed by other phyla such as actinobacteria and proteobacteria in ring necked pheasant and bacteroidetes in green necked pheasant. Bacillus was the most relatively abundant genus in both pheasants followed by Oceanobacillus and Teribacillus for ring necked pheasant and Lactobacillus for green necked pheasant. Because of their well-known beneficial characteristics, these genus warrants special attention. Bird droppings comprise germs from the urinary system, gut, and reproductive sites, making it difficult to research each anatomical site at the same time. We conclude that metagenomic analysis and classification provides baseline information of the pheasant fecal microbiome that plays a role in disease and health. 相似文献
4.
Octreotide is a synthetic analog of the peptide hormone somatostatin (SMS). A wide variety of tumors express enhanced numbers of SMS receptors, notably neuroendocrine tumors and lymphomas, but also some of the more common adenocarcinomas. Octreotide contains only eight amino acids, some of which are in the (D) configuration in order to enhance the stability of the molecule in vivo. Tyrosine and DTPA-containing analogs of octreotide have been synthesized and labeled with iodine-123 and indium-111, respectively, with the intention of targeting SMS receptor-containing tumors for diagnostic purposes. Both radiopharmaceuticals demonstrate a high sensitivity and specificity for these tumors, indicating a clinical role for these agents in management of these diseases. Lessons can be learned from the success of these agents when designing improved antibody-based molecules. Tumor uptake of radiolabeled octreotide is very rapid, occurring within minutes of administration. Blood clearance is also rapid, such that tumors are soon visible even in areas of high blood background. An interesting finding has been the differences between the pharmacokinetics of the iodinated and indium-labeled species. Although the majority of 123I-Tyr3-octreotide undergoes hepatobiliary excretion, 111In-DTPAPhe1-octreotide is eliminated predominantly by the kidneys. These results suggest that the smallest possible antibody-like tracers are likely to have advantages over native immunoglobulins and conventional Fab-like fragments. 相似文献
5.
Peter Henriksen Sebastian A. Wagner Brian T. Weinert Satyan Sharma Giedr? Ba?inskaja Michael Rehman André H. Juffer Tobias C. Walther Michael Lisby Chunaram Choudhary 《Molecular & cellular proteomics : MCP》2012,11(11):1510-1522
Post-translational modification of proteins by lysine acetylation plays important regulatory roles in living cells. The budding yeast Saccharomyces cerevisiae is a widely used unicellular eukaryotic model organism in biomedical research. S. cerevisiae contains several evolutionary conserved lysine acetyltransferases and deacetylases. However, only a few dozen acetylation sites in S. cerevisiae are known, presenting a major obstacle for further understanding the regulatory roles of acetylation in this organism. Here we use high resolution mass spectrometry to identify about 4000 lysine acetylation sites in S. cerevisiae. Acetylated proteins are implicated in the regulation of diverse cytoplasmic and nuclear processes including chromatin organization, mitochondrial metabolism, and protein synthesis. Bioinformatic analysis of yeast acetylation sites shows that acetylated lysines are significantly more conserved compared with nonacetylated lysines. A large fraction of the conserved acetylation sites are present on proteins involved in cellular metabolism, protein synthesis, and protein folding. Furthermore, quantification of the Rpd3-regulated acetylation sites identified several previously known, as well as new putative substrates of this deacetylase. Rpd3 deficiency increased acetylation of the SAGA (Spt-Ada-Gcn5-Acetyltransferase) complex subunit Sgf73 on K33. This acetylation site is located within a critical regulatory domain in Sgf73 that interacts with Ubp8 and is involved in the activation of the Ubp8-containing histone H2B deubiquitylase complex. Our data provides the first global survey of acetylation in budding yeast, and suggests a wide-ranging regulatory scope of this modification. The provided dataset may serve as an important resource for the functional analysis of lysine acetylation in eukaryotes.Lysine acetylation is a dynamic and reversible post-translational modification. Acetylation of lysines on their ε-amino group is catalyzed by lysine acetyltransferases (KATs1, also known as histone acetyltrasferases (HATs)), and reversed by lysine deacetylases (KDACs, also known as histone deacetylases (HDACs)) (1). The enzymatic machinery involved in lysine acetylation is evolutionary conserved in all forms of life (2–4). The role of acetylation has been extensively studied in the regulation of gene expression via modification of histones (5). Acetylation also plays important roles in controlling cellular metabolism (6–10), protein folding (11), and sister chromatid cohesion (12). Furthermore, acetylation has been implicated in regulating the beneficial effects of calorie restriction (13), a low nutrient diet without starvation, and aging. Based on these findings, it is proposed that the functional roles of acetylation in these processes are evolutionary conserved from yeast to mammals.Advancements in mass spectrometry (MS)-based proteomics have greatly facilitated identification of thousands of post-translational modification (PTM) sites in eukaryotic cells (14–18). Proteome-wide mapping of PTM sites can provide important leads for analyzing the functional relevance of individual sites and a systems-wide view of the regulatory scope of post-translational modifications. Also, large-scale PTM datasets are an important resource for the in silico analysis of PTMs, which can broaden the understanding of modification site properties and their evolutionary trajectories.The budding yeast Saccharomyces cerevisiae is a commonly used unicellular eukaryotic model organism. Yeast has been used in many pioneering “-omics” studies, including sequencing of the first eukaryotic genome (19), systems-wide genetic interactions analysis (20, 21), MS-based comprehensive mapping of a eukaryotic proteome (22), and proteome-wide analysis of protein-protein interactions (23, 24). In addition, S. cerevisiae has been extensively used to study the molecular mechanisms of acetylation. Many lysine acetyltransferases and deacetylases were discovered in this organism (2, 25), and their orthologs were subsequently identified in higher eukaryotes. Furthermore, the functional roles of many well-studied acetylation sites on histones are conserved from yeast to mammals. Recent data from human and Drosophila cells show that acetylation is present on many highly conserved metabolic enzymes (26–28). However, only a few dozen yeast acetylation sites are annotated in the Uniprot database. Given the presence of a well-conserved and elaborate acetylation machinery in yeast, we reasoned that many more acetylation sites exist in this organism that remained to be identified.Here we used high resolution mass spectrometry-based proteomics to investigate the scope of acetylation in S. cerevisiae. We identified about 4000 unique acetylation sites in this important model organism. Bioinformatic analysis of yeast acetylation sites and comparison with previously identified human and Drosophila acetylation sites indicates that many acetylation sites are evolutionary conserved. Furthermore, quantitative analysis of the Rpd3-regulated acetylation sites identified several nuclear proteins that showed increased acetylation in rpd3 knockout cells. Our results provide a systems-wide view of acetylation in budding yeast, and a rich dataset for functional analysis of acetylation sites in this organism. 相似文献
6.
Waqar Ahmad Bushra Ijaz Khadija Shabbiri Fayyaz Ahmed Sidra Rehman 《Journal of biomedical science》2017,24(1):76
Reactive oxidative species (ROS) toxicity remains an undisputed cause and link between Alzheimer’s disease (AD) and Type-2 Diabetes Mellitus (T2DM). Patients with both AD and T2DM have damaged, oxidized DNA, RNA, protein and lipid products that can be used as possible disease progression markers. Although the oxidative stress has been anticipated as a main cause in promoting both AD and T2DM, multiple pathways could be involved in ROS production. The focus of this review is to summarize the mechanisms involved in ROS production and their possible association with AD and T2DM pathogenesis and progression. We have also highlighted the role of current treatments that can be linked with reduced oxidative stress and damage in AD and T2DM. 相似文献
7.
The effects of Russell's viper venom on blood coagulation, platelets and the fibrinolytic enzyme system were studied in rabbits after injecting repeated doses of 0.05 MLD of the venom. Thrombocytopenia was the earliest change to appear. It was followed by rise in serum fibrinogen degradation products and prolongation of prothrombin time, activated partial thromboplastin time and thrombin time indicating a progressive consumption coagulopathy and activation of fibrinolysis. Red blood cell morphology was unchanged during the first three weeks; whereas the fragmentation appeared after the fourth week and it increased in severity with further envenomations, i.e. when chronic DIC was established. 相似文献
8.
9.
Md. Ashraful Alam Milan Skalicky Muhammad Rezaul Kabir Md. Monwar Hossain Md. Abdul Hakim Md. Siddikun Nabi Mandal Rabiul Islam Md. Babul Anwar Akbar Hossain Fahmy Hassan Amaal Mohammadein Muhammad Aamir Iqbal Marian Brestic Mohammad Anwar Hossain Khalid Rehman Hakeem Ayman EL Sabagh 《Phyton》2021,90(4):1301-1320
Globally among biotic stresses, diseases like blight, rust and blast constitute prime constraints for reducing wheat
productivity especially in Bangladesh. For sustainable productivity, the development of disease-resistant lines and
high yielding varieties is vital and necessary. This study was conducted using 122 advanced breeding lines of
wheat including 21 varieties developed by Bangladesh Wheat and Maize Research Institute (BAMRI) with aims
to identify genotypes having high yield potential and resistance to leaf blight, leaf rust and blast diseases. These
genotypes were evaluated for resistance against leaf blight and leaf rust at Dinajpur and wheat blast at Jashore
under field condition. Out of 122 genotypes tested, 20 lines were selected as resistant to leaf blight based on
the area under the diseases progress curve (AUDPC) under both irrigated timely sown (ITS) and irrigated late
sown (ILS) conditions. Forty-two genotypes were found completely free from leaf rust infection, 59 genotypes
were identified as resistant, and 13 genotypes were identified as moderately resistant to leaf rust. Eighteen genotypes were immune against wheat blast, 42 genotypes were categorized as resistant, and 26 genotypes were identified as moderately resistant to wheat blast. Molecular data revealed that the 16 genotypes showed a positive 2NS
segment among the 18 immune genotypes selected against wheat blast under field conditions. The genotypes
BAW 1322, BAW 1295, and BAW 1203 can be used as earlier maturing genotypes and the genotypes BAW
1372, BAW 1373, BAW 1297 and BAW 1364 can be used for lodging tolerant due to short plant height. The genotypes WMRI Gom 1, BAW 1349 and BAW 1350 can be selected for bold grain and the genotypes WMRI Gom 1,
BAW 1297, BAW 1377 can be used as high yielder for optimum seeding condition but genotypes BAW 1377
and BAW 1366 can be used for late sown condition. The selected resistant genotypes against specific diseases can be used in the further breeding program to develop wheat varieties having higher disease resistance and
yield potential. 相似文献
10.
Mahendran Ganesan Kumar Deepak Verma Sanjeet Kumar Chandran Ashish Warsi ·Zafar Iqbal Husain Zakir Afroz Shama Rout Prasant Kumar Rahman Laiq Ur 《Plant Cell, Tissue and Organ Culture》2021,146(2):423-423
Plant Cell, Tissue and Organ Culture (PCTOC) - 相似文献