全文获取类型
收费全文 | 481篇 |
免费 | 30篇 |
国内免费 | 1篇 |
专业分类
耳鼻咽喉 | 3篇 |
儿科学 | 10篇 |
妇产科学 | 5篇 |
基础医学 | 66篇 |
口腔科学 | 10篇 |
临床医学 | 31篇 |
内科学 | 110篇 |
皮肤病学 | 7篇 |
神经病学 | 30篇 |
特种医学 | 12篇 |
外科学 | 97篇 |
综合类 | 15篇 |
预防医学 | 22篇 |
眼科学 | 6篇 |
药学 | 51篇 |
中国医学 | 3篇 |
肿瘤学 | 34篇 |
出版年
2023年 | 4篇 |
2022年 | 11篇 |
2021年 | 17篇 |
2020年 | 10篇 |
2019年 | 14篇 |
2018年 | 12篇 |
2017年 | 5篇 |
2016年 | 15篇 |
2015年 | 13篇 |
2014年 | 14篇 |
2013年 | 30篇 |
2012年 | 28篇 |
2011年 | 30篇 |
2010年 | 25篇 |
2009年 | 24篇 |
2008年 | 39篇 |
2007年 | 31篇 |
2006年 | 38篇 |
2005年 | 18篇 |
2004年 | 21篇 |
2003年 | 11篇 |
2002年 | 14篇 |
2001年 | 17篇 |
2000年 | 13篇 |
1999年 | 7篇 |
1998年 | 4篇 |
1997年 | 5篇 |
1996年 | 4篇 |
1995年 | 9篇 |
1994年 | 1篇 |
1992年 | 4篇 |
1991年 | 3篇 |
1990年 | 1篇 |
1989年 | 3篇 |
1987年 | 2篇 |
1985年 | 4篇 |
1984年 | 3篇 |
1983年 | 3篇 |
1981年 | 1篇 |
1980年 | 2篇 |
1979年 | 1篇 |
1978年 | 1篇 |
排序方式: 共有512条查询结果,搜索用时 93 毫秒
111.
112.
113.
High fructose feeding in normal rats induces insulin resistance and also facilitates oxidative damage. The present study examines the effects of a spices mixture (SM) on oxidative stress markers and antioxidant potential in tissues of high fructose-fed insulin-resistant rats. Male Wistar rats received a semisynthetic diet containing either 60% fructose or 60% starch. SM administration at three different doses (10, 30, and 50 mg/day per rat) was initiated orally 15 days later and continued for the next 30 days. After the total experimental period of 45 days, peroxidation of lipids and antioxidant status in liver and kidney were quantified. Fructose-treated rats showed increased levels of peroxidation indices such as thiobarbituric acid-reactive substances and lipid hydroperoxides in tissues. The condition was associated with an inadequate antioxidant system. Administration of SM along with fructose diet reduced the levels of peroxidation markers in tissues and improved the antioxidant status. The positive effect of SM on the oxidant-antioxidant balance could be attributed to the active constituents of the different spices present in the mixture. 相似文献
114.
Lack of SHPTP1 results in src-family kinase hyperactivation and thymocyte hyperresponsiveness. 总被引:7,自引:0,他引:7
下载免费PDF全文
![点击此处可从《Proceedings of the National Academy of Sciences of the United States of America》网站下载免费的PDF全文](/ch/ext_images/free.gif)
U Lorenz K S Ravichandran S J Burakoff B G Neel 《Proceedings of the National Academy of Sciences of the United States of America》1996,93(18):9624-9629
Protein tyrosine phosphorylation and dephosphorylation are key regulatory events in T-cell receptor (TCR) signaling. We investigated the role of the tyrosine phosphatase SHPTP1 in TCR signaling by analysis of TCR signal transduction in motheaten (me/me) mice, which lack SHPTP1 expression. As revealed by flow cytometric analysis, thymocyte development was normal in me/me mice. However, me/me thymocytes hyperproliferated (3-to 5-fold) in response to TCR stimulation, whereas their response to interleukin 2 stimulation was unchanged compared with normal thymocytes. TCR-induced hyperproliferation of me/me thymocytes was reproduced in purified single-positive thymocytes. Moreover, me/me thymocytes produced increased amounts of interleukin 2 production upon TCR stimulation. Biochemical analysis revealed that, in response to TCR or TCR/CD4 stimulation, thymocytes lacking SHPTP1 showed increased tyrosyl phosphorylation of several cellular substrates, which correlated with increased activation of the src-family kinases Lck and Fyn. Taken together, our data suggest that SHPTP1 is an important negative regulator of TCR signaling, acting at least in part to inactivate Lck and Fyn. 相似文献
115.
Activation of the serine/threonine kinase Akt and the regulation of its activation are recognized as critical in controlling proliferative/survival signals via many hematopoietic receptors. In B lymphocytes, the B-cell receptor (BCR)-mediated activation of Akt is attenuated by co-cross-linking of BCR with the inhibitory receptor Fc gamma RIIB1, and the binding of the SH2 domain-containing inositol phosphatase, SHIP, to Fc gamma RIIB1. Because SHIP dephosphorylates phosphatidylinositol 3,4,5-trisphosphate (PIP3) and activation of Akt requires PIP3, the destruction of this phospholipid has been proposed as the mechanism for Akt inhibition. However, upstream kinases that activate Akt, such as PDK1, also require PIP3 for activation. In this report, we addressed whether SHIP inhibits Akt directly at the level of Akt recruitment to the membrane, indirectly through PDK recruitment/phosphorylation of Akt, or both. We generated stable B-cell lines expressing a regulatable, but constitutively membrane-bound Akt that still required PDK-dependent phosphorylation for activation. Several lines of evidence suggested that activation of this membrane-targeted Akt is not inhibited by Fc gamma RIIB1/SHIP and that PDK is not a target for SHIP-mediated inhibition. These data demonstrate that SHIP inhibits Akt primarily through regulation of Akt membrane localization. We also observed during these studies that Fc gamma RIIB1/SHIP does not inhibit p70(S6k) activation, even though several other PIP3-dependent events were down-regulated. Because the enhanced activation of Akt in the absence of SHIP correlates with hyperproliferation in the myeloid lineage, our data have implications for SHIP and Akt-dependent regulation of proliferation in the hematopoietic lineage. (Blood. 2000;96:1449-1456) 相似文献
116.
117.
Jishana Jamaldeen Aneesh Basheer Akhil Chandra Sarma Ravichandran Kandasamy 《The Australasian medical journal》2015,8(2):41-46
Background
The prevalence, degree, and patterns of hearing loss associated with chronic kidney disease (CKD) reported by various studies differ significantly. The effects of haemodialysis and duration of disease on hearing loss remain unclear.Aims
The aim of this study was to determine the prevalence and degree of hearing loss in CKD patients on haemodialysis.Methods
This study included 120 CKD patients on haemodialysis. Information regarding age, gender, duration of disease, subjective hearing loss, exposure to ototoxic drugs, comorbidities like diabetes, hypertension, and hypothyroidism, renal functions, electrolytes and number of haemodialysis sessions received were obtained. An equal number of age and sex matched controls were used to determine prevalence of hearing loss in CKD patients after subjecting both groups to pure tone audiometry. We compared CKD patients with and without hearing loss for association of hearing loss with disease duration, number of haemodialysis, and blood parameters.Results
Hearing loss was present in 41.7 per cent of CKD patients, significantly higher than controls (p=0.001), and was mild in the majority of patients. Impairment was noted across high and low frequencies of audiometric testing. Median duration of disease was the same (18 months) among CKD patients with and without hearing loss (p=0.62). CKD patients with hearing loss received 72 haemodialysis compared to 122 sessions by those without hearing loss (p=0.04).Conclusion
Mild sensorineural hearing loss is common in CKD. Hearing loss has no specific pattern as it prevails at high and low frequencies. Hearing loss may be inversely associated with the number of haemodialysis sessions but not with duration of disease. 相似文献118.
119.
Evidence for a role for the phosphotyrosine-binding domain of Shc in interleukin 2 signaling. 总被引:6,自引:0,他引:6
下载免费PDF全文
![点击此处可从《Proceedings of the National Academy of Sciences of the United States of America》网站下载免费的PDF全文](/ch/ext_images/free.gif)
K S Ravichandran V Igras S E Shoelson S W Fesik S J Burakoff 《Proceedings of the National Academy of Sciences of the United States of America》1996,93(11):5275-5280
Stimulation via the T-cell growth factor interleukin 2 (IL-2) leads to tyrosine phosphorylation of Shc, the interaction of Shc with Grb2, and the Ras GTP/GDP exchange factor, mSOS. Shc also coprecipitates with the IL-2 receptor (IL-2R), and therefore, may link IL-2R to Ras activation. We have further characterized the Shc-IL-2R interaction and have made the following observations. (i) Among the two phosphotyrosine-interaction domains present in Shc, the phosphotyrosine-binding (PTB) domain, rather than its SH2 domain, interacts with the tyrosine-phosphorylated IL-2R beta chain. Moreover, the Shc-PTB domain binds a phosphopeptide derived from the IL-2R beta chain (corresponding to residues surrounding Y338, SCFTNQGpYFF) with high affinity. (ii) In vivo, mutant IL-2R beta chains lacking the acidic region of IL-2Rbeta (which contains Y338) fail to phosphorylate Shc. Furthermore, when wild type or mutant Shc proteins that lack the PTB domain were expressed in the IL-2-dependent CTLL-20 cell line, an intact Shc-PTB domain was required for Shc phosphorylation by the IL-2R, which provides further support for a Shc-PTB-IL-2R interaction in vivo. (iii) PTB and SH2 domains of Shc associate with different proteins in IL-2- and T-cell-receptor-stimulated lysates, suggesting that Shc, through the concurrent use of its two different phosphotyrosine-binding domains, could assemble multiple protein complexes. Taken together, our in vivo and in vitro observations suggest that the PTB domain of Shc interacts with Y338 of the IL-2R and provide evidence for a functional role for the Shc-PTB domain in IL-2 signaling. 相似文献
120.
Biomimetic fetal rotation bioreactor for engineering bone tissues—Effect of cyclic strains on upregulation of osteogenic gene expression
下载免费PDF全文
![点击此处可从《Journal of tissue engineering and regenerative medicine》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Akhilandeshwari Ravichandran Feng Wen Jing Lim Mark Seow Khoon Chong Jerry K.Y. Chan Swee‐Hin Teoh 《Journal of tissue engineering and regenerative medicine》2018,12(4):e2039-e2050
Cells respond to physiological mechanical stresses especially during early fetal development. Adopting a biomimetic approach, it is necessary to develop bioreactor systems to explore the effects of physiologically relevant mechanical strains and shear stresses for functional tissue growth and development. This study introduces a multimodal bioreactor system that allows application of cyclic compressive strains on premature bone grafts that are cultured under biaxial rotation (chamber rotation about 2 axes) conditions for bone tissue engineering. The bioreactor is integrated with sensors for dissolved oxygen levels and pH that allow real‐time, non‐invasive monitoring of the culture parameters. Mesenchymal stem cells‐seeded polycaprolactone–β‐tricalcium phosphate scaffolds were cultured in this bioreactor over 2 weeks in 4 different modes—static, cyclic compression, biaxial rotation, and multimodal (combination of cyclic compression and biaxial rotation). The multimodal culture resulted in 1.8‐fold higher cellular proliferation in comparison with the static controls within the first week. Two weeks of culture in the multimodal bioreactor utilizing the combined effects of optimal fluid flow conditions and cyclic compression led to the upregulation of osteogenic genes alkaline phosphatase (3.2‐fold), osteonectin (2.4‐fold), osteocalcin (10‐fold), and collagen type 1 α1 (2‐fold) in comparison with static cultures. We report for the first time, the independent and combined effects of mechanical stimulation and biaxial rotation for bone tissue engineering using a bioreactor platform with non‐invasive sensing modalities. The demonstrated results show leaning towards the futuristic vision of using a physiologically relevant bioreactor system for generation of autologous bone grafts for clinical implantation. 相似文献