全文获取类型
收费全文 | 683篇 |
免费 | 27篇 |
出版年
2023年 | 4篇 |
2022年 | 10篇 |
2021年 | 12篇 |
2020年 | 13篇 |
2019年 | 13篇 |
2018年 | 13篇 |
2017年 | 7篇 |
2016年 | 11篇 |
2015年 | 25篇 |
2014年 | 35篇 |
2013年 | 30篇 |
2012年 | 42篇 |
2011年 | 41篇 |
2010年 | 29篇 |
2009年 | 19篇 |
2008年 | 31篇 |
2007年 | 36篇 |
2006年 | 40篇 |
2005年 | 33篇 |
2004年 | 29篇 |
2003年 | 45篇 |
2002年 | 31篇 |
2001年 | 11篇 |
2000年 | 13篇 |
1999年 | 14篇 |
1998年 | 9篇 |
1997年 | 2篇 |
1996年 | 3篇 |
1994年 | 5篇 |
1992年 | 7篇 |
1991年 | 6篇 |
1990年 | 5篇 |
1989年 | 4篇 |
1988年 | 5篇 |
1987年 | 3篇 |
1986年 | 5篇 |
1985年 | 6篇 |
1984年 | 8篇 |
1983年 | 2篇 |
1982年 | 3篇 |
1981年 | 6篇 |
1980年 | 3篇 |
1979年 | 11篇 |
1978年 | 3篇 |
1977年 | 8篇 |
1974年 | 2篇 |
1973年 | 2篇 |
1971年 | 3篇 |
1970年 | 5篇 |
1969年 | 2篇 |
排序方式: 共有710条查询结果,搜索用时 15 毫秒
141.
Shipra Bhansali Anil Bhansali Pinaki Dutta Rama Walia Veena Dhawan 《Journal of cellular and molecular medicine》2020,24(5):2832-2846
Impaired mitochondrial autophagy (mitophagy) and NLRP3 inflammasome activation have been incriminated in the pathogenesis of T2DM. Metformin besides being an insulin sensitizer also induces autophagy; however, its effect on mitophagy and NLRP3 activation in patients with T2DM still remains elusive. Forty-five drug-naïve T2DM patients with HbA1C 7%-9% (53-75 mmol/mol) were randomly assigned to receive either metformin, voglibose, or placebo for 3 months, and were also recommended for lifestyle intervention programme (n = 15 each). Mitochondrial oxidative stress (MOS) parameters, qPCR and immunoblotting of mitophagy-related markers (PINK1, PARKIN, MFN2, NIX, LC3-II, LAMP2), p-AMPKα (T172), and NLRP3 proteins, as well as transmission electron microscopy (TEM) for assessing mitochondrial morphology were performed in the mononuclear cells of study patients. Both metformin and voglibose showed a similar efficacy towards the reduction in HbA1c and MOS indices. However, multivariate ANCOVA divulged that mRNA and protein expression of mitophagy markers, NLRP3 and p-AMPKα (T172), were significantly increased only with metformin therapy. Moreover, PINK1 expression displayed a significant positive association with HOMA-β indices, and TEM studies further confirmed reduced distortions in mitochondrial morphology in the metformin group only. Our observations underscore that metformin upregulates mitophagy and subsequently ameliorates the altered mitochondrial morphology and function, independent of its glucose-lowering effect. Further, restoration of normal mitochondrial phenotype may improve cellular function, including β-cells, which may prevent further worsening of hyperglycaemia in patients with T2DM. 相似文献
142.
143.
144.
P P Singh S Singh V C Dhawan W Haq K B Mathur G P Dutta R C Srimal B N Dhawan 《Journal of biological regulators and homeostatic agents》1991,5(4):142-146
Methionine-enkephalin (M-Enk) and its analogue compound 82/205 (10(-5) and 10(-6) M) inhibited elaboration of Plasmodium cynomolgi total antigens soluble in culture medium (P.c.SA)-induced colony-stimulating factors (CSFs) by monkey blood monocyte-derived macrophages, in vitro. Paradoxically, lower concentrations (10(-7)-10(-9) M) of both the peptides greatly augmented CSFs elaboration; 82/205 appeared to be nearly 2.3-fold more potent. Naloxone (10(-5) M) pretreatment of macrophages inhibited only the M-Enk- and 82/205-induced enhanced CSFs elaboration, suggesting an opiate receptors-mediated mechanism of action. None of the peptides or naloxone (10(-5)-10(-9) M) had any direct effect on the CSF elaboration by unstimulated macrophages. 相似文献
145.
Yao-Te Huang Chung-Hung Liu Yao-Chih Yang Ritu Aneja Su-Ying Wen Chih-Yang Huang Wei-Wen Kuo 《Journal of cellular physiology》2019,234(8):13557-13570
The prevalence of chronic hyperglycemia and its complications, imposing a critical burden on the worldwide economy and the global healthcare system, is a pressing issue. Mounting evidence indicates that oxidative stress and hypoxia, two noticeable features of hyperglycemia, play a joint crucial role in mediating cellular apoptosis. However, the underlying detailed molecular mechanism remains elusive. Triggered by the observation that insulin-like growth factor (IGF1)-binding protein 3 (IGFBP3) can mediate, in renal cells, high-glucose-induced apoptosis by elevating oxidative stress, we wish to, in this study, know whether or not the similar scenario holds in cardiac cells and, if so, to find its relevant molecular key players, thereby dissecting the underlying molecular pathway. Specifically, we used a combination of three different cellular sources (H9c2 cells, diabetic rats, and neonatal rat ventricular cardiomyocytes) as our model systems of study. We made use of Co-IP assay and western blot analysis in conjunction with loss-of-function reasoning, gain-of-function logic, and inhibitor treatment as our main analytical tools. As a result, briefly, our main findings are that hyperglycemia can induce cardiac IGFBP3 overexpression and secretion, that high levels of IGFBP3 can sequester IGF1 from IGF1 survival pathway, leading to apoptosis, and that IGFBP3 gene upregulation is hypoxia-inducible factor (HIF)1α-dependent and reactive oxygen species dependent. Piecing these findings together allows us to propose the improved molecular regulatory mechanism. In conclusion, we have established the molecular roles of IGFBP3, HIF1, and prolyl hydroxylase domain in connecting oxidative stress with hypoxia and in cellular apoptosis under hyperglycemia. 相似文献
146.
Multivariate analytical routines have become increasingly popular in the study of cerebral function in health and in disease states. Spatial covariance analysis of functional neuroimaging data has been used to identify and validate characteristic topographies associated with specific brain disorders. Voxel-wise correlations can be used to assess similarities and differences that exist between covariance topographies. While the magnitude of the resulting topographical correlations is critical, statistical significance can be difficult to determine in the setting of large data vectors (comprised of over 100,000 voxel weights) and substantial autocorrelation effects. Here, we propose a novel method to determine the p-value of such correlations using pseudo-random network simulations. 相似文献
147.
148.
A growth regulator (G) occurs at high concentrations in adult leaves of E. grandis Maiden. Low concentrations of G are present in juvenile leaves of this species and also in adult leaves of some other Myrtaceae. Low concentrations of G (5×10–6 and 10–5 M) promote rooting in mung-bean cuttings and elongation in Avena coleoptile sections; high concentrations (5×10–4 M) inhibit. These and other bioassay results indicate that G may have auxin-like activity. 相似文献
149.
Verma Preeti Varshney Ritu Yadav Shiv Pratap Singh Kar Bibekananda Roy Partha Sharma Ashwani K. 《The protein journal》2022,41(3):381-393
The Protein Journal - A class of plant defense and storage proteins, including Putranjiva roxburghii PNP protein (PRpnp), belongs to PNP-UDP family. The PRpnp and related plant proteins contain a... 相似文献
150.
Ritu Malhotra James P Warne Eduardo Salas Allison W Xu Jayanta Debnath 《Autophagy》2015,11(1):145-154
The autophagy-related proteins ATG12 and ATG5 form a covalent complex essential for autophagy. Here, we demonstrate that ATG12 has distinct functions from ATG5 in pro-opiomelanocortin (POMC)-expressing neurons. Upon high-fat diet (HFD) consumption, mice lacking Atg12 in POMC-positive neurons exhibit accelerated weight gain, adiposity, and glucose intolerance, which is associated with increased food intake, reduced ambulation, and decreased LEP/leptin sensitivity. Importantly, although genetic deletion of either Atg12 or Atg5 renders POMC neurons autophagy-deficient, mice lacking Atg5 in POMC neurons do not exhibit these phenotypes. Hence, we propose nonautophagic functions for ATG12 in POMC neurons that counteract excessive weight gain in response to HFD consumption. 相似文献