全文获取类型
收费全文 | 589篇 |
免费 | 54篇 |
出版年
2024年 | 3篇 |
2023年 | 11篇 |
2022年 | 21篇 |
2021年 | 31篇 |
2020年 | 16篇 |
2019年 | 21篇 |
2018年 | 23篇 |
2017年 | 21篇 |
2016年 | 30篇 |
2015年 | 21篇 |
2014年 | 42篇 |
2013年 | 57篇 |
2012年 | 46篇 |
2011年 | 55篇 |
2010年 | 35篇 |
2009年 | 22篇 |
2008年 | 35篇 |
2007年 | 18篇 |
2006年 | 33篇 |
2005年 | 23篇 |
2004年 | 17篇 |
2003年 | 12篇 |
2002年 | 12篇 |
2001年 | 1篇 |
2000年 | 3篇 |
1999年 | 6篇 |
1998年 | 2篇 |
1996年 | 9篇 |
1994年 | 1篇 |
1993年 | 3篇 |
1992年 | 2篇 |
1991年 | 5篇 |
1990年 | 1篇 |
1989年 | 1篇 |
1988年 | 1篇 |
1976年 | 1篇 |
1973年 | 1篇 |
1972年 | 1篇 |
排序方式: 共有643条查询结果,搜索用时 15 毫秒
1.
Fourier transform infrared (FTIR) spectroscopic imaging is an emerging microscopy modality for clinical histopathologic diagnoses as well as for biomedical research. Spectral data recorded in this modality are indicative of the underlying, spatially resolved biochemical composition but need computerized algorithms to digitally recognize and transform this information to a diagnostic tool to identify cancer or other physiologic conditions. Statistical pattern recognition forms the backbone of these recognition protocols and can be used for highly accurate results. Aided by biochemical correlations with normal and diseased states and the power of modern computer-aided pattern recognition, this approach is capable of combating many standing questions of traditional histology-based diagnosis models. For example, a simple diagnostic test can be developed to determine cell types in tissue. As a more advanced application, IR spectral data can be integrated with patient information to predict risk of cancer, providing a potential road to precision medicine and personalized care in cancer treatment. The IR imaging approach can be implemented to complement conventional diagnoses, as the samples remain unperturbed and are not destroyed. Despite high potential and utility of this approach, clinical implementation has not yet been achieved due to practical hurdles like speed of data acquisition and lack of optimized computational procedures for extracting clinically actionable information rapidly. The latter problem has been addressed by developing highly efficient ways to process IR imaging data but remains one that has considerable scope for progress. Here, we summarize the major issues and provide practical considerations in implementing a modified Bayesian classification protocol for digital molecular pathology. We hope to familiarize readers with analysis methods in IR imaging data and enable researchers to develop methods that can lead to the use of this promising technique for digital diagnosis of cancer. 相似文献
2.
cdc28-1N is a conditional allele that has normal G1 (Start) function but confers a mitotic defect. We have isolated seven genes that in high dosage suppress the growth defect of cdc28-1N cells but not of Start-defective cdc28-4 cells. Three of these (CLB1, CLB2, and CLB4) encode proteins strongly homologous to G2-specific B-type cyclins. Another gene, CLB3, was cloned using PCR, CLB1 and CLB2 encode a pair of closely related proteins; CLB3 and CLB4 encode a second pair. Neither CLB1 nor CLB2 is essential; however, disruption of both is lethal and causes a mitotic defect. Furthermore, the double mutant cdc28-1N clb2::LEU2 is nonviable, whereas cdc28-4 clb2::LEU2 is viable, suggesting that the cdc28-1N protein may be defective in its interaction with B-type cyclins. Our results are consistent with CDC28 function being required in both G1 and mitosis. Its mitotic role, we believe, involves interaction with a family of at least four G2-specific cyclins. 相似文献
3.
Characterization of de novo duplications in eight patients by using fluorescence in situ hybridization with chromosome-specific DNA libraries.
下载免费PDF全文
![点击此处可从《American journal of human genetics》网站下载免费的PDF全文](/ch/ext_images/free.gif)
J Leana-Cox S Levin R Surana E Wulfsberg C L Keene L J Raffel B Sullivan S Schwartz 《American journal of human genetics》1993,52(6):1067-1073
Fluorescence in situ hybridization (FISH) with chromosome-specific DNA libraries was performed on samples from eight patients with de novo chromosomal duplications. In five cases, the clinical phenotype and/or cytogenetic evaluations suggested a likely origin of the duplicated material. In the remaining three cases, careful examination of the GTG-banding pattern indicated multiple possible origins; hybridization with more than one chromosome-specific library was performed on two of these cases. In all cases, FISH conclusively identified the chromosomal origin of the duplicated material. In addition, the hybridization pattern was useful in quantitatively delineating the duplication in two cases. 相似文献
4.
Fermentation of biomass-generated producer gas to ethanol 总被引:3,自引:0,他引:3
Datar RP Shenkman RM Cateni BG Huhnke RL Lewis RS 《Biotechnology and bioengineering》2004,86(5):587-594
The development of low-cost, sustainable, and renewable energy sources has been a major focus since the 1970s. Fuel-grade ethanol is one energy source that has great potential for being generated from biomass. The demonstration of the fermentation of biomass-generated producer gas to ethanol is the major focus of this article in addition to assessing the effects of producer gas on the fermentation process. In this work, producer gas (primarily CO, CO(2), CH(4), H(2), and N(2)) was generated from switchgrass via gasification. The fluidized-bed gasifier generated gas with a composition of 56.8% N(2), 14.7% CO, 16.5% CO(2), 4.4% H(2), and 4.2% CH(4). The producer gas was utilized in a 4-L bioreactor to generate ethanol and other products via fermentation using a novel clostridial bacterium. The effects of biomass-generated producer gas on cell concentration, hydrogen uptake, and acid/alcohol production are shown in comparison with "clean" bottled gases of similar compositions for CO, CO(2), and H(2). The successful implementation of generating producer gas from biomass and then fermenting the producer gas to ethanol was demonstrated. Several key findings following the introduction of producer gas included: (1) the cells stopped growing but were still viable, (2) ethanol was primarily produced once the cells stopped growing (ethanol is nongrowth associated), (3) H(2) utilization stopped, and (4) cells began growing again if "clean" bottled gases were introduced following exposure to the producer gas. 相似文献
5.
Anand Kumar Seema Singh Satyajit Pradhan Ram C Shukla Mumtaz A Ansari Tej B Singh Rohit Shyam Saroj Gupta 《World journal of surgical oncology》2007,5(1):1-6
Background
Von Hippel-Lindau (VHL) disease is an autosomal dominant inherited disease. It is relatively recent that type 2C was identified as a separate group solely presenting with pheochromocytomas. As an illustration, an interesting case is presented of a pregnant woman with refractory hypertension. It proved to be the first manifestation of bilateral pheochromocytomas. The family history may indicate the diagnosis, but only identification of a germ line mutation in the DNA of a patient will confirm carriership.Case presentation
A 27 year pregnant patient with intra uterine growth retardation presented with hypertension and pre-eclampsia. Magnetic resonance imaging revealed bilateral adrenal pheochromocytoma. She underwent laparoscopic adrenelectomy and a missense mutation (Gly93Ser) in exon 1 of the VHL gene on chromosome 3 (p25 - p26) was shown in the patient, her father and her daughter confirming the diagnosis of VHL.Conclusion
In almost all VHL families molecular genetic analysis of DNA will demonstrate an inherited mutation. Because of the involvement in several organs, periodic clinical evaluation should take place in a well coordinated, multidisciplinary setting. VHL disease can be classified into several subtypes. VHL type 2C patients present with pheochromocytomas without evidence of haemangioblastomas in the central nervous system and/or retina and a low risk of renal cell carcinoma. Therefore, in such families, periodic clinical screening can be focussed on pheochromocytomas. 相似文献6.
Glucose transporter isotypes switch in T-antigen-transformed pancreatic beta cells growing in culture and in mice.
下载免费PDF全文
![点击此处可从《Molecular and cellular biology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
M Tal B Thorens M Surana N Fleischer H F Lodish D Hanahan S Efrat 《Molecular and cellular biology》1992,12(1):422-432
High-level expression of the low-Km glucose transporter isoform GLUT-1 is characteristic of many cultured tumor and oncogene-transformed cells. In this study, we tested whether induction of GLUT-1 occurs in tumors in vivo. Normal mouse beta islet cells express the high-Km (approximately 20 mM) glucose transporter isoform GLUT-2 but not the low-Km (1 to 3 mM) GLUT-1. In contrast, a beta cell line derived from an insulinoma arising in a transgenic mouse harboring an insulin-promoted simian virus 40 T-antigen oncogene (beta TC3) expressed very low levels of GLUT-2 but high levels of GLUT-1. GLUT-1 protein was not detectable on the plasma membrane of islets or tumors of the transgenic mice but was induced in high amounts when the tumor-derived beta TC3 cells were grown in tissue culture. GLUT-1 expression in secondary tumors formed after injection of beta TC3 cells into mice was reduced. Thus, high-level expression of GLUT-1 in these tumor cells is characteristic of culture conditions and is not induced by the oncogenic transformation; indeed, overnight culture of normal pancreatic islets causes induction of GLUT-1. We also investigated the relationship between expression of the different glucose transporter isoforms by islet and tumor cells and induction of insulin secretion by glucose. Prehyperplastic transgenic islet cells that expressed normal levels of GLUT-2 and no detectable GLUT-1 exhibited an increased sensitivity to glucose, as evidenced by maximal insulin secretion at lower glucose concentrations, compared with that exhibited by normal islets. Further, hyperplastic islets and primary and secondary tumors expressed low levels of GLUT-2 and no detectable GLUT-1 on the plasma membrane; these cells exhibited high basal insulin secretion and responded poorly to an increase in extracellular glucose. Thus, abnormal glucose-induced secretion of insulin in prehyperplastic islets in mice was independent of changes in GLUT-2 expression and did not require induction of GLUT-1 expression. 相似文献
7.
Rohit K. Thapa Filipe M. Clemente Jason Moran Felipe Garcia-Pinillos Aaron T. Scanlan Rodrigo Ramirez-Campillo 《Biology of sport / Institute of Sport》2023,40(1):321
The aim of this study was to compare the effects of small-sided soccer games (SSSGs) and traditional warm-up (TWU) routines on physical fitness qualities in soccer players. Following a between-subject, randomized design, amateur-level soccer players were assigned to a SSSG warm-up (n = 10; age: 19.3 ± 2.8 years) or TWU group (n = 10; age: 19.3 ± 2.4 years). Players completed multiple trials of 10-m and 30-m linear sprints, change-of-direction speed (CODS) tests, and countermovement jumps (CMJ) prior to and following the warm-up routine. Separate mixed ANOVAs were performed to assess group effects (SSSG vs. TWU), time effects within each group (pre- vs. post-warm-up), and their interaction for each physical fitness quality. No significant interaction effects were observed for any dependent variable. Significant improvements were evident between baseline and follow-up measurements for 10-m sprint time (p = 0.002, Hedges’ g effect size [g] = 0.59) and CMJ variables (height: p = 0.016, g = 0.20; power: p = 0.003, g = 0.19; force: p = 0.002, g = 0.14) in the TWU group and for CODS performance time (p = 0.012, g = 0.51) and CMJ variables (height: p < 0.001, g = 0.46; power: p = 0.002, g = 0.35; force: p = 0.001, g = 0.27) in the SSSG warm-up group. Both SSSG and TWU protocols improved selected physical fitness qualities with SSSG more effective at improving CODS and CMJ performance, and TWU more effective at improving linear speed. Soccer coaches may choose between SSSG or traditional warm-up activities according to player needs and preferences; however, the superior effects of SSSG suggest it might offer greater benefits than TWU in preparing players for optimal physical output. 相似文献
8.
Sandhini Saha Rohit Verma Chandan Kumar Bhoj Kumar Amit Kumar Dey Milan Surjit Sivaram V. S. Mylavarapu Tushar Kanti Maiti 《Cell death & disease》2022,13(6)
Nutrient surplus and consequent free fatty acid accumulation in the liver cause hepatosteatosis. The exposure of free fatty acids to cultured hepatocyte and hepatocellular carcinoma cell lines induces cellular stress, organelle adaptation, and subsequent cell death. Despite many studies, the mechanism associated with lipotoxicity and subsequent cell death still remains poorly understood. Here, we have used the proteomics approach to circumvent the mechanism for lipotoxicity using hepatocellular carcinoma cells as a model. Our quantitative proteomics data revealed that ectopic lipids accumulation in cells severely affects the ubiquitin-proteasomal system. The palmitic acid (PA) partially lowered the expression of deubiquitinating enzyme USP7 which subsequently destabilizes p53 and promotes mitotic entry of cells. Our global phosphoproteomics analysis also provides strong evidence of an altered cell cycle checkpoint proteins’ expression that abrogates early G2/M checkpoints recovery with damaged DNA and induced mitotic catastrophe leading to hepatocyte death. We observe that palmitic acid prefers apoptosis-inducing factor (AIF) mediated cell death by depolarizing mitochondria and translocating AIF to the nucleus. In summary, the present study provides evidence of PA-induced hepatocellular death mediated by deubiquitinase USP7 downregulation and subsequent mitotic catastrophe.Subject terms: Apoptosis, Protein-protein interaction networks 相似文献
9.