全文获取类型
收费全文 | 248篇 |
免费 | 7篇 |
出版年
2024年 | 1篇 |
2023年 | 5篇 |
2022年 | 11篇 |
2021年 | 19篇 |
2020年 | 8篇 |
2019年 | 8篇 |
2018年 | 11篇 |
2017年 | 12篇 |
2016年 | 11篇 |
2015年 | 18篇 |
2014年 | 9篇 |
2013年 | 18篇 |
2012年 | 12篇 |
2011年 | 17篇 |
2010年 | 5篇 |
2009年 | 11篇 |
2008年 | 9篇 |
2007年 | 9篇 |
2006年 | 7篇 |
2005年 | 9篇 |
2004年 | 4篇 |
2003年 | 7篇 |
2002年 | 4篇 |
2001年 | 1篇 |
2000年 | 4篇 |
1999年 | 1篇 |
1998年 | 3篇 |
1997年 | 2篇 |
1993年 | 1篇 |
1990年 | 1篇 |
1989年 | 2篇 |
1987年 | 1篇 |
1985年 | 5篇 |
1984年 | 7篇 |
1983年 | 1篇 |
1975年 | 1篇 |
排序方式: 共有255条查询结果,搜索用时 15 毫秒
121.
McGowan EM Alling N Jackson EA Yagoub D Haass NK Allen JD Martinello-Wilks R 《PloS one》2011,6(6):e20623
Endocrine resistance is a major problem with anti-estrogen treatments and how to overcome resistance is a major concern in the clinic. Reliable measurement of cell viability, proliferation, growth inhibition and death is important in screening for drug treatment efficacy in vitro. This report describes and compares commonly used proliferation assays for induced estrogen-responsive MCF-7 breast cancer cell cycle arrest including: determination of cell number by direct counting of viable cells; or fluorescence SYBR®Green (SYBR) DNA labeling; determination of mitochondrial metabolic activity by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay; assessment of newly synthesized DNA using 5-ethynyl-2′-deoxyuridine (EdU) nucleoside analog binding and Alexa Fluor® azide visualization by fluorescence microscopy; cell-cycle phase measurement by flow cytometry. Treatment of MCF-7 cells with ICI 182780 (Faslodex), FTY720, serum deprivation or induction of the tumor suppressor p14ARF showed inhibition of cell proliferation determined by the Trypan Blue exclusion assay and SYBR DNA labeling assay. In contrast, the effects of treatment with ICI 182780 or p14ARF-induction were not confirmed using the MTS assay. Cell cycle inhibition by ICI 182780 and p14ARF-induction was further confirmed by flow cytometric analysis and EdU-DNA incorporation. To explore this discrepancy further, we showed that ICI 182780 and p14ARF-induction increased MCF-7 cell mitochondrial activity by MTS assay in individual cells compared to control cells thereby providing a misleading proliferation readout. Interrogation of p14ARF-induction on MCF-7 metabolic activity using TMRE assays and high content image analysis showed that increased mitochondrial activity was concomitant with increased mitochondrial biomass with no loss of mitochondrial membrane potential, or cell death. We conclude that, whilst p14ARF and ICI 182780 stop cell cycle progression, the cells are still viable and potential treatments utilizing these pathways may contribute to drug resistant cells. These experiments demonstrate how the combined measurement of metabolic activity and DNA labeling provides a more reliable interpretation of cancer cell response to treatment regimens. 相似文献
122.
The discrete modeling formalism of René Thomas is a well known approach for the modeling and analysis of Biological Regulatory Networks (BRNs). This formalism uses a set of parameters which reflect the dynamics of the BRN under study. These parameters are initially unknown but may be deduced from the appropriately chosen observed dynamics of a BRN. The discrete model can be further enriched by using the model checking tool HyTech along with delay parameters. This paves the way to accurately analyse a BRN and to make predictions about critical trajectories which lead to a normal or diseased response. In this paper, we apply the formal discrete and hybrid (discrete and continuous) modeling approaches to characterize behavior of the BRN associated with MyD88-adapter-like (MAL)--a key protein involved with innate immune response to infections. In order to demonstrate the practical effectiveness of our current work, different trajectories and corresponding conditions that may lead to the development of cerebral malaria (CM) are identified. Our results suggest that the system converges towards hyperinflammation if Bruton's tyrosine kinase (BTK) remains constitutively active along with pre-existing high cytokine levels which may play an important role in CM pathogenesis. 相似文献
123.
Nadadur RD Umar S Wong G Eghbali M Iorga A Matori H Partow-Navid R Eghbali M 《Journal of applied physiology (Bethesda, Md. : 1985)》2012,112(1):149-158
Acute respiratory distress syndrome is a pulmonary disease with a mortality rate of ~40% and 75,000 deaths annually in the United States. Mechanical ventilation restores airway patency and gas transport but leads to ventilator-induced lung injury. Furthermore, surfactant replacement therapy is ineffective due to surfactant delivery difficulties and deactivation by vascular proteins leaking into the airspace. Here, we demonstrated that surfactant function can be substantially improved (up to 50%) in situ in an in vitro pulmonary airway model using unconventional flows that incorporate a short-term retraction of the air-liquid interface, leading to a net decrease in cellular damage. Computational fluid dynamic simulations provided insights into this method and demonstrated the physicochemical hydrodynamic foundation for the improved surfactant microscale transport and mobility. This study may provide a starting point for developing novel ventilation waveforms to improve surfactant function in edematous airways. 相似文献
124.
125.
Umar Twahir Laura Molina Andrew Ozarowski Alexander Angerhofer 《Biochemistry and Biophysics Reports》2015
Oxalate decarboxylase, a bicupin enzyme coordinating two essential manganese ions per subunit, catalyzes the decomposition of oxalate into carbon dioxide and formate in the presence of oxygen. Current efforts to elucidate its catalytic mechanism are focused on EPR studies of the Mn. We report on a new immobilization strategy linking the enzyme's N-terminal His6-tag to a Zn-loaded immobilized metal affinity resin. Activity is lowered somewhat due to the expected crowding effect. High-field EPR spectra of free and immobilized enzyme show that the resin affects the coordination environment of the active site Mn ions only minimally. The immobilized preparation was used to study the effect of varying pH on the same sample. Repeated freeze-thaw cycles lead to break down of the resin beads and some enzyme loss from the sample. However, the EPR signal increases due to higher packing efficiency on the sample column. 相似文献
126.
Proteomic characterization of microdissected breast tissue environment provides a protein‐level overview of malignant transformation
下载免费PDF全文
![点击此处可从《Proteomics》网站下载免费的PDF全文](/ch/ext_images/free.gif)
René B. H. Braakman Christoph Stingl Madeleine M. A. Tilanus‐Linthorst Carolien H. M. van Deurzen Mieke A. M. Timmermans Marcel Smid John A. Foekens Theo M. Luider John W. M. Martens Arzu Umar 《Proteomics》2017,17(5)
Both healthy and cancerous breast tissue is heterogeneous, which is a bottleneck for proteomics‐based biomarker analysis, as it obscures the cellular origin of a measured protein. We therefore aimed at obtaining a protein‐level interpretation of malignant transformation through global proteome analysis of a variety of laser capture microdissected cells originating from benign and malignant breast tissues. We compared proteomic differences between these tissues, both from cells of epithelial origin and the stromal environment, and performed string analysis. Differences in protein abundances corresponded with several hallmarks of cancer, including loss of cell adhesion, transformation to a migratory phenotype, and enhanced energy metabolism. Furthermore, despite enriching for (tumor) epithelial cells, many changes to the extracellular matrix were detected in microdissected cells of epithelial origin. The stromal compartment was heterogeneous and richer in the number of fibroblast and immune cells in malignant sections, compared to benign tissue sections. Furthermore, stroma could be clearly divided into reactive and nonreactive based on extracellular matrix disassembly proteins. We conclude that proteomics analysis of both microdissected epithelium and stroma gives an additional layer of information and more detailed insight into malignant transformation. 相似文献
127.
Mohammed Yagoub Jomaa Muhammed Altaf Saeed Ahmad Gaurav Bhatia Jatinder Singh Saleh Altuwaijri Anvarhusein A. Isab 《Biometals》2017,30(5):787-795
Seven new platinum(II) complexes (1–7) of triethylphosphine (Et3P) and thiones (L) with general formula, cis-[Pt(Et3P)2(L)2]Cl2 were prepared and characterized by elemental analysis, FTIR and NMR (1H, 13C & 31P) measurements. The analytical and spectroscopic data suggested the formation of the desired complexes. The complexes were tested for in vitro cytotoxicity against four cell lines: Hela (human cervical adenocarcinoma), MCF-7 (human breast carcinoma), A549 (human lung carcinoma), and HTC15 (human colon carcinoma). The anticancer activity values of compounds 1–6 are much better than cisplatin and carboplatin as indicated by their IC50 values. 相似文献
128.
Umar Wazir Kinan Mokbel Amtul Carmichael Kefah Mokbel 《Cellular & molecular biology letters》2017,22(1):20
Background
Clinicians use clinical and pathological parameters, such as tumour size, grade and nodal status, to make decisions on adjuvant treatments for breast cancer. However, therapeutic decisions based on these features tend to vary due to their subjectivity. Computational and mathematical algorithms were developed using clinical outcome data from breast cancer registries, such as Adjuvant! Online and NHS PREDICT. More recently, assessments of molecular profiles have been applied in the development of better prognostic tools.Methods
Based on the available literature on online registry-based tools and genomic assays, we evaluated whether these online tools could be valid and accurate alternatives to genomic and molecular profiling of the individual breast tumour in aiding therapeutic decisions, particularly in patients with early ER-positive breast cancer.Results and conclusions
Early breast cancer is currently considered a systemic disease and a complex ecosystem with behaviour determined by the complex genetic and molecular signatures of the tumour cells, mammary stem cells, microenvironment and host immune system. We anticipate that molecular profiling will continue to evolve, expanding beyond the primary tumour to include the tumour microenvironment, cancer stem cells and host immune system. This should further refine therapeutic decisions and optimise clinical outcome.This article was specially invited by the editors and represents work by leading researchers.129.
Ahmad VU Abbasi MA Hussain H Akhtar MN Farooq U Fatima N Choudhary MI 《Phytochemistry》2003,63(2):217-220
One new phenolic glycoside named benzoylsalireposide (1) along with one known phenolic glycoside named salireposide (2) have been isolated from Symplocos racemosa. Four other known compounds i.e. beta-amyrin (3), oleonolic acid (4), beta-sitosterol (5) and beta-sitosterol glycoside (6) were also isolated from this plant. The structure elucidation of the isolated compounds was based primarily on 1D- and 2D-NMR analysis, including COSY, HMQC, and HMBC correlations. The compound 1 and 2 showed inhibitory activity against snake venom phosphodiesterase I. 相似文献
130.
Rashid UJ Paterok D Koglin A Gohlke H Piehler J Chen JC 《The Journal of biological chemistry》2007,282(18):13824-13832
Gene silencing mediated by RNA interference requires the sequence-specific recognition of target mRNA by the endonuclease Argonaute, the primary enzymatic component of the RNA-induced silencing complex. We report the crystal structure of Aquifex aeolicus Argonaute, refined at 3.2A resolution. Relative to recent Argonaute structures, a 24 degrees reorientation of the PAZ domain in our structure opens a basic cleft between the N-terminal and PAZ domains, exposing the guide strand binding pocket of PAZ. This rearrangement leads to a branched, Y-shaped system of grooves that extends through the molecule and merges in a central channel containing the catalytic residues. A 5.5-ns molecular dynamics simulation of Argonaute shows a strong tendency of the PAZ and N-terminal domains to be mobile. Binding of single-stranded DNA to Argonaute monitored by total internal reflection fluorescence spectroscopy shows biphasic kinetics, also indicative of domain rearrangement upon DNA binding. Conformational rearrangement of the PAZ domain may therefore be critical for the catalytic cycle of Argonaute and the RNA-induced silencing complex. 相似文献