全文获取类型
收费全文 | 589篇 |
免费 | 58篇 |
国内免费 | 1篇 |
出版年
2023年 | 3篇 |
2021年 | 10篇 |
2020年 | 17篇 |
2019年 | 43篇 |
2018年 | 29篇 |
2017年 | 8篇 |
2016年 | 12篇 |
2015年 | 12篇 |
2014年 | 16篇 |
2013年 | 32篇 |
2012年 | 18篇 |
2011年 | 10篇 |
2010年 | 21篇 |
2009年 | 10篇 |
2008年 | 22篇 |
2007年 | 19篇 |
2006年 | 21篇 |
2005年 | 19篇 |
2004年 | 10篇 |
2003年 | 20篇 |
2002年 | 15篇 |
2001年 | 29篇 |
2000年 | 12篇 |
1999年 | 19篇 |
1998年 | 21篇 |
1997年 | 8篇 |
1996年 | 20篇 |
1995年 | 18篇 |
1994年 | 5篇 |
1993年 | 12篇 |
1992年 | 13篇 |
1991年 | 7篇 |
1990年 | 10篇 |
1989年 | 16篇 |
1988年 | 9篇 |
1987年 | 8篇 |
1986年 | 3篇 |
1985年 | 5篇 |
1984年 | 7篇 |
1983年 | 4篇 |
1982年 | 6篇 |
1981年 | 4篇 |
1980年 | 7篇 |
1979年 | 5篇 |
1978年 | 3篇 |
1976年 | 2篇 |
1974年 | 5篇 |
1973年 | 4篇 |
1972年 | 4篇 |
1922年 | 2篇 |
排序方式: 共有648条查询结果,搜索用时 31 毫秒
41.
Alfred J. Lewy MD. PhD Jonathan S. Emens Bryan J. Lefler Krista Yuhas Angela R. Jackman 《Chronobiology international》2013,30(6):1093-1106
The specific circadian role proposed for endogenous melatonin production was based on a study of sighted people who took low pharmacological doses (500 µg) of this chemical signal for the “biological night”: the magnitude and direction of the induced phase shifts were dependent on what time of day exogenous melatonin was administered and were described by a phase‐response curve that turned out to be the opposite of that for light. We now report that lower (physiological) doses of up to 300 µg can entrain (synchronize) free‐running circadian rhythms of 10 totally blind subjects that would otherwise drift later each day. The resulting log‐linear dose‐response curve in the physiological range adds support for a circadian function of endogenous melatonin in humans. Efficacy of exogenous doses in the physiological range are of clinical significance for totally blind people who will need to take melatonin daily over their entire lifetimes in order to remain entrained to the 24 h day. Left untreated, their free‐running endocrine, metabolic, behavioral, and sleep/wake cycles can be almost as burdensome as not having vision. 相似文献
42.
43.
Ying-Chun Liang MD Yu-Peng Wu MD Xiao-Dong Li MD Shao-Hao Chen MD Xiao-Jian Ye MD Xue-Yi Xue MD Ning Xu MD 《Journal of cellular physiology》2019,234(12):23243-23255
The effective treatment of urethral stricture remains a medical problem. The use of proinflammatory cytokines as stimuli to improve the reparative efficacy of mesenchymal stem cells (MSCs) towards damaged tissues represents an evolving field of investigation. However, the therapeutic benefits of this strategy in the treatment of urethral stricture remain unknown. Here, we enriched exosomes derived from human umbilical cord-derived MSCs pretreated with or without tumor necrosis factor alpha (TNF-α) to evaluate their therapeutic effects in an in vivo model of TGFβ1-induced urethral stricture. Male Sprague-Dawley rats received sham (saline) or TGFβ1 injections to urethral tissues followed by incisions in the urethra. Animals in the TGFβ1 injection (urethral fibrosis) cohort were subsequently injected with vehicle control, or with exosomes derived from MSCs cultured with or without TNF-α. After 4 weeks, rats underwent ultrasound evaluation and, following euthanasia, urethral tissues were harvested for histological and molecular analysis. In vitro, the effects of MSC-derived exosomes on fibroblast secretion of collagen and cytokines were studied by enzyme-linked immunosorbent assay (ELISA), quantitative real-time polymerase chain reaction (qRT-PCR), and western blot analysis. Exosomes derived from MSCs pretreated with TNF-α were more effective in suppressing urethral fibrosis and stricture than exosomes from untreated MSCs. We found that miR-146a, an anti-inflammatory miRNA, was strongly upregulated in TNF-α-stimulated MSCs and was selectively packaged into exosomes. Moreover, miR-146a-containing exosomes were taken up by fibroblasts and inhibited fibroblast activation and associated inflammatory responses, a finding that may underlie the therapeutic mechanism for suppression of urethral stricture. Inhibition of miR-146a in TNF-α-treated MSCs partially reduced antifibrotic effects and increased the release of proinflammatory factors of exosomes derived from these cells. Together these findings demonstrate that exosomes derived from TNF-α-treated MSCs are of therapeutic benefit in urethral fibrosis, suggesting that this strategy may have utility as an adjuvant therapy in the treatment of urethral stricture diseases. 相似文献
44.
45.
Xianchen Huang MD Zhao Liu MD PhD Liming Shen MD Yiqi Jin MD Guoxiong Xu MD Zhixuan Zhang MD Changwen Fang MD Wenxian Guan MD PhD Changjian Liu MD PhD 《Journal of cellular biochemistry》2019,120(6):10031-10042
In varicose veins, vascular smooth muscle cells (VSMCs) often show abnormal proliferative and migratory rates and phenotypic transition. This study aimed to investigate whether microRNA (miR)-202 and its potential target, peroxisome proliferator–activated receptor-γ coactivator-1α (PGC-1α), were involved in VSMC phenotypic transition. miR-202 expression was analyzed in varicose veins and in VSMCs conditioned with platelet-derived growth factor. The effect of miR-202 on cell proliferation and migration was assessed. Furthermore, contractile marker SM-22α, synthetic markers vimentin and collagen I, and PGC-1α were analyzed by Western blot analysis. The modulation of PGC-1α expression by miR-202 was also evaluated. In varicose veins and proliferative VSMCs, miR-202 expression was upregulated, with decreased SM-22α expression and increased vimentin and collagen I expression. Transfection with a miR-202 mimic induced VSMC proliferation and migration, whereas a miR-202 inhibitor reduced cell proliferation and migration. miR-202 mimic constrained luciferase activity in HEK293 cells that were cotransfected with the PGC-1α 3′-untranslated region (3′-UTR) but not those with mutated 3′-UTR. miR-202 suppressed PGC-1α protein expression, with no influence on its messenger RNA expression. PGC-1α mediated VSMC phenotypic transition and was correlated with reactive oxygen species production. In conclusion, miR-202 affects VSMC phenotypic transition by targeting PGC-1α expression, providing a novel target for varicose vein therapy. 相似文献
46.
47.
Yichen Meng MD Jun Ma MD Tao Lin MD Heng Jiang MD Ce Wang MD Fu Yang MD PhD Xuhui Zhou MD 《Journal of cellular biochemistry》2019,120(10):18236-18245
The genetic etiology of adolescent idiopathic scoliosis (AIS) remains obscure. Whole-genome sequencing was performed in four members of one family. Then, we performed a rigorous computational analysis to determine the deleterious effects of the identified variants. Furthermore, the structural differences between the native hepatocyte growth factor (HGF) protein and a protein encoded by an HGF variant containing one mutation (p.T596M) were analyzed using molecular dynamic stimulation. A novel heterozygous mutation (p.T596M) within the HGF gene was identified and found to cosegregate with scoliosis phenotypes in three affected family members. Subsequent modeling and structure-based analyses supported the theory that this mutation is functionally deleterious. Functional analyses demonstrated that the HGF p.T596 M mutation changed the ability of the HGF protein to be secreted and impaired migration and invasion in HEK293T cells. Furthermore, an HGF knockdown zebrafish model exhibited a curly tailed phenotype. Mutation in HGF is associated with an autosomal dominant pattern of inheritance of AIS. This finding increases our understanding of the genetic heterogeneity of AIS. 相似文献
48.
Qi Zou MD Chong-Jie Zhang MD Yu-Zhong Yan MD Zhi-Jun Min MD Chun-Sheng Li MD 《Journal of cellular biochemistry》2019,120(11):18650-18658
This study aims to explore the ability of magnetic resonance imaging (MRI) in mucin 1 (MUC1) modified superparamagnetic iron oxide nanoparticle (SPION) targeting human pancreatic cancer (PC). The MUC1 target-directed probe was prepared through MUC1 conjugated to SPION using the chemical method to assess its physiochemical characteristics, including hydration diameter, surface charge, and magnetic resonance signal. The cytotoxicity of MUC1-USPION was verified by MTS assay. BxPC-3 was cultured with MUC1-USPION and SPION in different concentrations. The combined condition of the targeted probes and cells were observed through Prussian blue staining. The nude mice model of pancreatic cancer was established to investigate the application of the probe. MRI was performed to determine the intensity of the signal of the transplanted tumor, while immunohistochemistry and Western blot analysis were performed to detect the expression of MUC1 after taking the transplanted tumor specimen. The particle size of the prepared molecular probe was 63.5 ± 3.2 nm, and the surface charge was 10.2 mV. Furthermore, the probe solution could significantly reduce the MRI at T2, and the magnetic resonance transverse relaxation rate (ΔR2) has a linear relationship with the concentration of iron in the solution. The cell viability of MUC1-USPION in different concentrations revealed no statistical difference, according to the MTS assay. In vitro, the MRI demonstrated decreased T2WI signal intensity in both groups, especially the targeting group. In vivo, MUC1 could selectively accumulate in the nude mice model, and significantly reduce the T2 signal strength. In subsequent experiments, the expression of MUC1 was high in pancreatic cancer tissues, but low in normal pancreatic tissues, as determined by immunohistochemistry and Western blot analysis. The prepared samples can be combined with pancreatic cancer tissue specificity by in vivo imaging, providing reliable early in vivo imaging data for disease diagnosis. 相似文献
49.
50.
Eli S. P. Patterson Roy A. Sanderson Michael D. Eyre 《Journal of Applied Entomology》2019,143(4):430-440
Crop rotation systems in organic and conventional farming systems differ in crop types, management and duration. However, changes in arthropod communities over the entire rotation system are poorly understood, as many studies have surveyed only single years or have not covered the entire rotation period. Here, we describe changes in arthropods in two contrasting systems at a split organic‐conventional farm: an 8‐year organically managed rotation with five crops and a 5‐year conventionally managed rotation with three crops. Arthropods were classified into three functional groups, representing epigeal predators, foliar predators/parasitoids and herbivores/pollinators. Epigeal predators were particularly reduced by soil tillage which occurred annually in the conventional rotation, but was intermittent in the organic. Arthropods were most abundant on the conventional rotation, but most taxonomically diverse on the organic. In the conventional system, all functional groups showed a cyclical change in their taxonomic composition that closely matched the crop rotation sequence, whereas in the organic rotation, the cycle was less clear. Whilst the current year's crop type was the major determinant of arthropod community composition, there was a significant “lag effect” for many taxa from the preceding year's crop. Our results suggest that both the amounts of soil tillage (e.g., in no‐till systems) and crop rotation order have major impacts on arthropods in agroecosystems. Rotations with excessive soil tillage are likely to reduce the abundance of some groups of beneficial arthropods, especially epigeal predators. 相似文献