全文获取类型
收费全文 | 1426篇 |
免费 | 192篇 |
出版年
2021年 | 20篇 |
2020年 | 12篇 |
2018年 | 16篇 |
2016年 | 22篇 |
2015年 | 43篇 |
2014年 | 54篇 |
2013年 | 64篇 |
2012年 | 75篇 |
2011年 | 80篇 |
2010年 | 48篇 |
2009年 | 46篇 |
2008年 | 61篇 |
2007年 | 60篇 |
2006年 | 54篇 |
2005年 | 59篇 |
2004年 | 61篇 |
2003年 | 52篇 |
2002年 | 61篇 |
2001年 | 14篇 |
2000年 | 15篇 |
1999年 | 16篇 |
1998年 | 27篇 |
1997年 | 18篇 |
1996年 | 14篇 |
1995年 | 12篇 |
1994年 | 17篇 |
1992年 | 15篇 |
1991年 | 19篇 |
1990年 | 12篇 |
1989年 | 14篇 |
1988年 | 16篇 |
1987年 | 15篇 |
1986年 | 13篇 |
1984年 | 13篇 |
1983年 | 16篇 |
1982年 | 17篇 |
1981年 | 25篇 |
1980年 | 18篇 |
1978年 | 12篇 |
1977年 | 14篇 |
1976年 | 17篇 |
1974年 | 14篇 |
1973年 | 16篇 |
1971年 | 14篇 |
1970年 | 13篇 |
1969年 | 15篇 |
1968年 | 18篇 |
1967年 | 12篇 |
1964年 | 16篇 |
1963年 | 15篇 |
排序方式: 共有1618条查询结果,搜索用时 31 毫秒
81.
Alterations in immunological and neurological gene expression patterns in Alzheimer's disease tissues 总被引:2,自引:0,他引:2
Weeraratna AT Kalehua A Deleon I Bertak D Maher G Wade MS Lustig A Becker KG Wood W Walker DG Beach TG Taub DD 《Experimental cell research》2007,313(3):450-461
Microarray technology was utilized to isolate disease-specific changes in gene expression by sampling across inferior parietal lobes of patients suffering from late onset AD or non-AD-associated dementia and non-demented controls. Primary focus was placed on understanding how inflammation plays a role in AD pathogenesis. Gene ontology analysis revealed that the most differentially expressed genes related to nervous system development and function and neurological disease followed by genes involved in inflammation and immunological signaling. Pathway analysis also implicated a role for chemokines and their receptors, specifically CXCR4 and CCR3, in AD. Immunohistological analysis revealed that these chemokine receptors are upregulated in AD patients. Western analysis demonstrated an increased activation of PKC, a downstream mediator of chemokine receptor signaling, in the majority of AD patients. A very specific cohort of genes related to amyloid beta accumulation and clearance were found to be significantly altered in AD. The most significantly downregulated gene in this data set was the endothelin converting enzyme 2 (ECE2), implicated in amyloid beta clearance. These data were subsequently confirmed by real-time PCR and Western blot analysis. Together, these findings open up new avenues of investigation and possible therapeutic strategies targeting inflammation and amyloid clearance in AD patients. 相似文献
82.
83.
Wong Dorothy Plumb James Talab Hosamiddine Kurdi Mouhamad Pokhrel Keshav Oelkers Peter 《Mycopathologia》2019,184(2):213-226
Mycopathologia - Perturbing ergosterol synthesis has been previously shown to reduce the virulence of Candida albicans. We tested the hypothesis that further altering cell membrane composition by... 相似文献
84.
Panagiotis Tsakiroglou James Weber Sharon Ashworth Cristian Del Bo Dorothy Klimis-Zacas 《Journal of cellular biochemistry》2019,120(7):11056-11067
The present study investigates the effect of anthocyanin (ACN), phenolic acid (PA) fractions, and their combination (ACNs:PAs) from wild blueberry powder (Vaccinum angustifolium) on the speed of endothelial cell migration, gene expression, and protein levels of RAC1 and RHOA associated with acute exposure to different concentrations of ACNs and PAs. Time-lapse videos were analyzed and endothelial cell speed was calculated. Treatment with ACNs at 60 μg/mL inhibited endothelial cell migration rate ( P ≤ 0.05) while treatment with PAs at 0.002 μg/mL ( P ≤ 0.0001), 60 μg/mL ( P ≤ 0.0001), and 120 μg/mL ( P ≤ 0.01) significantly increased endothelial cell migration rate compared with control. Moreover, exposure of HUVECs to ACNs:PAs at 8:8 μg/mL ( P ≤ 0.05) and 60:60 μg/mL increased ( P ≤ 0.001) endothelial cell migration. Gene expression of RAC1 and RHOA significantly increased 2 hours after exposure with all treatments. No effect of the above fractions was observed on the protein levels of RAC1 and RHOA. Findings suggest that endothelial cell migration is differentially modulated based on the type of blueberry extract (ACN or PA fraction) and is concentration-dependent. Future studies should determine the mechanism of the differential action of the above fractions on endothelial cell migration. 相似文献
85.
86.
EDA-A1 and EDA-A2 are members of the tumor necrosis factor family of ligands. The products of alternative splicing of the ectodysplasin (EDA) gene, EDA-A1 and EDA-A2 differ by an insertion of two amino acids and bind to distinct receptors. The longer isoform, EDA-A1, binds to EDAR and plays an important role in sweat gland, hair, and tooth development; mutations in EDA, EDAR, or the downstream adaptor EDARADD cause hypohidrotic ectodermal dysplasia. EDA-A2 engages the receptor XEDAR, but its role in the whole organism is less clear. We have generated XEDAR-deficient mice by gene targeting and transgenic mice expressing secreted forms of EDA-A1 or EDA-A2 downstream of the skeletal muscle-specific myosin light-chain 2 or skin-specific keratin 5 promoter. Mice lacking XEDAR were indistinguishable from their wild-type littermates, but EDA-A2 transgenic mice exhibited multifocal myodegeneration. This phenotype was not observed in the absence of XEDAR. Skeletal muscle in EDA-A1 transgenic mice was unaffected, but their sebaceous glands were hypertrophied and hyperplastic, consistent with a role for EDA-A1 in the development of these structures. These data indicate that XEDAR-transduced signals are dispensable for development of ectoderm-derived organs but might play a role in skeletal muscle homeostasis. 相似文献
87.
88.
Wrigley DM 《Anaerobe》2004,10(5):295-300
The effect a common fecal organism, Bacteroides fragilis, has on the sporulation of Clostridium perfringens, an organism linked to some cases of antibiotic associated diarrhea, was examined. Established B. fragilis cultures significantly decreased the number of heat resistant spores formed by C. perfringens ATCC 12915 and increased the number of vegetative cells. To determine if short-chain fatty acids (SCFA), fermentation products of B. fragilis, inhibited sporulation, the SCFA were added to sporulation broth. Sporulation decreased in the presence of acetate, isobutyrate, isovalerate, and succinate. Vegetative cell number for C. perfringens decreased in the cultures with isobutyrate. Propionate did not affect sporulation or vegetative cell number. The data support the hypothesis that the decrease in short-chain fatty acid concentration following antibiotic therapy predisposes patients to diarrheas caused by C. perfringens. 相似文献
89.
Liu J Masurekar MR Vatner DE Jyothirmayi GN Regan TJ Vatner SF Meggs LG Malhotra A 《American journal of physiology. Heart and circulatory physiology》2003,285(6):H2587-H2591
Aging and diabetes mellitus (DM) both affect the structure and function of the myocardium, resulting in increased collagen in the heart and reduced cardiac function. As part of this process, hyperglycemia is a stimulus for the production of advanced glycation end products (AGEs), which covalently modify proteins and impair cell function. The goals of this study were first to examine the combined effects of aging and DM on hemodynamics and collagen types in the myocardium in 12 dogs, 9-12 yr old, and second to examine the effects of the AGE cross-link breaker phenyl-4,5-dimethylthazolium chloride (ALT-711) on myocardial collagen protein content, aortic stiffness, and left ventricular (LV) function in the aged diabetic heart. The alloxan model of DM was utilized to study the effects of DM on the aging heart. DM induced in the aging heart decreased LV systolic function (LV ejection fraction fell by 25%), increased aortic stiffness, and increased collagen type I and type III protein content. ALT-711 restored LV ejection fraction, reduced aortic stiffness and LV mass with no reduction in blood glucose level (199 +/- 17 mg/dl), and reversed the upregulation of collagen type I and type III. Myocardial LV collagen solubility (%) increased significantly after treatment with ALT-711. These data suggest that an AGE cross-link breaker may have a therapeutic role in aged patients with DM. 相似文献
90.
Adriamycin tolerant human mesothelioma cell lines derived from a single tumor prior to either chemotherapy or radiation therapy and a susceptible cell line were investigated. Not only was growth resistant to low doses of adriamycin but an unusual pattern of resistance was encountered in which cells seemed to better tolerate high adriamycin doses than intermediate doses. The differential growth susceptibility of the tolerant lines compared to A549 lung carcinoma and the bimodal dose response correlated with differences in the specific activity of a plasma membrane-associated NADH oxidase (NOX). Plasma membrane fractions of high purity were isolated by aqueous two-phase partition and assayed directly. The NADH oxidase activity of the plasma membranes for the susceptible cell line was maximally inhibited by 1 microM adriamycin whereas the NADH oxidase activity of the tolerant lines was less and was maximally inhibited by 0.1 microM adriamycin with 1 and 10 microM adriamycin being less inhibitory than 0.1 microM adriamycin. The findings suggest a relationship between the growth response to adriamycin of the adriamycin tolerant mesothelioma lines and the activity of the plasma membrane-associated NADH oxidase activity of the cell surface in these cell lines. 相似文献