全文获取类型
收费全文 | 1078篇 |
免费 | 65篇 |
国内免费 | 1篇 |
专业分类
1144篇 |
出版年
2023年 | 15篇 |
2022年 | 37篇 |
2021年 | 57篇 |
2020年 | 23篇 |
2019年 | 22篇 |
2018年 | 41篇 |
2017年 | 42篇 |
2016年 | 41篇 |
2015年 | 77篇 |
2014年 | 70篇 |
2013年 | 96篇 |
2012年 | 105篇 |
2011年 | 97篇 |
2010年 | 54篇 |
2009年 | 48篇 |
2008年 | 57篇 |
2007年 | 52篇 |
2006年 | 45篇 |
2005年 | 33篇 |
2004年 | 31篇 |
2003年 | 30篇 |
2002年 | 30篇 |
2001年 | 5篇 |
2000年 | 3篇 |
1999年 | 2篇 |
1998年 | 2篇 |
1997年 | 5篇 |
1996年 | 4篇 |
1995年 | 3篇 |
1994年 | 1篇 |
1992年 | 1篇 |
1989年 | 1篇 |
1985年 | 1篇 |
1982年 | 1篇 |
1981年 | 1篇 |
1979年 | 4篇 |
1978年 | 1篇 |
1977年 | 1篇 |
1976年 | 1篇 |
1973年 | 1篇 |
1971年 | 2篇 |
1965年 | 1篇 |
排序方式: 共有1144条查询结果,搜索用时 15 毫秒
91.
92.
93.
94.
Harun Patel Rahul Pawara Iqrar Ansari Harsha Jadhav Sanjay Surana 《Journal of receptor and signal transduction research》2013,33(5-6):393-412
AbstractCardiotoxicity is one amongst the adverse effect of Osimertinib delineate in clinical trials and related to escalating doses. To triumph over the drawbacks of Osimertinib, in this study, we tend to delineate the design, synthesis, in vitro biological analysis of a series of novel reversible selective T790M inhibitors with minimal cardiotoxicity. Amongst the virtually sorted compounds; compound 18 and 74 have been located to be the foremost active compounds of the series with IC50 value of 0.88, 0.92?μM in cellular assay and 0.56, 0.62?μM in enzymatic assay, against double mutant L858R/T790M EGFR. Additionally, they showed much less affinity toward wild-type (WT)-EGFR with minimal cardiotoxicity. 相似文献
95.
Deshmukh R Zeng Y Furci LM Huang HW Morgan BN Sander S Alontaga AY Bunce RA Moënne-Loccoz P Rivera M Wilks A 《Biochemistry》2005,44(42):13713-13723
Heme oxygenases from the bacterial pathogens Neisseriae meningitidis (nm-HO) and Pseudomonas aeruginosa (pa-HO) share significant sequence identity (37%). In nm-HO, biliverdin IXalpha is the sole product of the reaction, whereas pa-HO yields predominantly biliverdin IXdelta. We have previously shown by NMR that the in-plane conformation of the heme in pa-HO is significantly different from that of nm-HO as a result of distinct interactions of the heme propionates with the protein scaffold [Caignan, G. A., Deshmukh, R., Wilks, A., Zeng, Y., Huang, H. W., Moenne-Loccoz, P., Bunce, R. A., Eastman, M. A., and Rivera, M. (2002) J. Am. Chem. Soc. 124, 14879-14892]. In the report presented here, we have extended these studies to investigate the role of the distal helix by preparing a chimera of nm-HO (nm-HOch), in which distal helix residues 107-142 of nm-HO have been replaced with the corresponding residues of the delta-regioselective pa-HO (112-147). Electronic absorption spectra, resonance Raman and FTIR spectroscopic studies confirm that the orientation and hydrogen bonding properties of the proximal His ligand are not significantly altered in the chimera relative those of the wild-type proteins. The catalytic turnover of the nm-HOch-heme complex yields almost exclusively alpha-biliverdin and a small but reproducible amount of delta-biliverdin. NMR spectroscopic studies reveal that the altered regioselectivity in the chimeric protein likely stems from a dynamic equilibrium between two alternate in-plane conformations of the heme (in-plane heme disorder). Replacement of K16 with Ala and Met31 with Lys in the chimeric protein in an effort to tune key polypeptide-heme propionate contacts largely stabilizes the in-plane conformer conducive to delta-meso hydroxylation. 相似文献
96.
Shankar Prinja Pankaj Bahuguna P. V. M. Lakshmi Tushar Mokashi Arun Kumar Aggarwal Manmeet Kaur K. Rahul Reddy Rajesh Kumar 《PloS one》2014,9(10)
Background
Emergency referral services (ERS) are being strengthened in India to improve access for institutional delivery. We evaluated a publicly financed and privately delivered model of ERS in Punjab state, India, to assess its extent and pattern of utilization, impact on institutional delivery, quality and unit cost.Methods
Data for almost 0.4 million calls received from April 2012 to March 2013 was analysed to assess the extent and pattern of utilization. Segmented linear regression was used to analyse month-wise data on number of institutional deliveries in public sector health facilities from 2008 to 2013. We inspected ambulances in 2 districts against the Basic Life Support (BLS) standards. Timeliness of ERS was assessed for determining quality. Finally, we computed economic cost of implementing ERS from a health system perspective.Results
On an average, an ambulance transported 3–4 patients per day. Poor and those farther away from the health facility had a higher likelihood of using the ambulance. Although the ERS had an abrupt positive effect on increasing the institutional deliveries in the unadjusted model, there was no effect on institutional delivery after adjustment for autocorrelation. Cost of operating the ambulance service was INR 1361 (USD 22.7) per patient transported or INR 21 (USD 0.35) per km travelled.Conclusion
Emergency referral services in Punjab did not result in a significant change in public sector institutional deliveries. This could be due to high baseline coverage of institutional delivery and low barriers to physical access. Choice of interventions for reduction in Maternal Mortality Ratio (MMR) should be context-specific to have high value for resources spent. The ERS in Punjab needs improvement in terms of quality and reduction of cost to health system. 相似文献97.
Clarke MB Wright R Irwin D Bose S Van Rheen Z Birari R Stenmark KR McCord JM Nozik-Grayck E 《Free radical biology & medicine》2010,49(12):2032-2039
Delivery of recombinant superoxide dismutase to the lung is limited by its short half-life and poor tissue penetration. We hypothesized that a chimeric protein, SOD2/3, containing the enzymatic domain of manganese superoxide dismutase (SOD2) and the heparan-binding domain of extracellular superoxide dismutase (SOD3), would allow for the delivery of more sustained lung and pulmonary vascular antioxidant activity compared to SOD2. We administered SOD2/3 to rats by intratracheal (i.t.), intraperitoneal (i.p.), or intravenous (i.v.) routes and evaluated the presence, localization, and activity of lung SOD2/3 1 day later using Western blot, immunohistochemistry, and SOD activity gels. The effect of i.t. SOD2/3 on the pulmonary and systemic circulation was studied in vivo in chronically catheterized rats exposed to acute hypoxia. Active SOD2/3 was detected in lung 1 day after i.t. administration but not detected after i.p. or i.v. SOD2/3 administration or i.t. SOD2. The physiologic response to acute hypoxia, vasoconstriction in the pulmonary circulation and vasodilation in the systemic circulation, was enhanced in rats treated 1 day earlier with i.t. SOD2/3. These findings indicate that i.t. administration of SOD2/3 effectively delivers sustained enzyme activity to the lung as well as pulmonary circulation and has a longer tissue half-life compared to native SOD2. Further testing in models of chronic lung or pulmonary vascular diseases mediated by excess superoxide should consider the longer tissue half-life of SOD2/3 as well as its potential systemic vascular effects. 相似文献
98.
An amperometric biosensor was developed to estimate galactose in human blood serum. Monolayers of poly(3-hexyl thiophene) were placed on glass plates coated with indium tin oxide formed by dispensing a mixed solution of stearic acid in chloroform on to a water sub-phase. Galactose oxidase was mixed with poly(3-hexyl thiophene)/stearic acid in chloroform and dispensed on to the air-water interface of Langmuir-Blodgett trough. These monolayers were transferred on to glass plates which were used as working electrodes with platinum as a reference electrode. The amperometric galactose biosensor thus fabricated had a linear response from 0.05 to 0.5 g galactose l(-1) in blood serum. The normal level in blood is < 0.05 g galactose l(-1) in adults and 0-0.2 g galactose l(-1) in infants. In case of galactosemia, this increases to above 0.2 g galactose l(-1) in infants. 相似文献
99.
Richa Tiwari Nirmalya Ganguli Hunain Alam Indrajit Sahu Chella Krishna Vadivel Shruti Sinha Shweta Patel Sayli Nitin Jamghare Sanjay Bane Rahul Thorat Subeer S. Majumdar Milind M. Vaidya 《Cell biology international》2021,45(8):1720-1732
Keratin 8/18, the predominant keratin pair of simple epithelia, is known to be aberrantly expressed in several squamous cell carcinomas (SCCs), where its expression is often correlated with increased invasion, neoplastic progression, and poor prognosis. The majority of keratin 8/18 structural and regulatory functions are governed by posttranslational modifications, particularly phosphorylation. Apart from filament reorganization, cellular processes including cell cycle, cell growth, cellular stress, and apoptosis are known to be orchestrated by K8 phosphorylation at specific residues in the head and tail domains. Even though deregulation of K8 phosphorylation at two significant sites (Serine73/Serine431) has been implicated in neoplastic progression of SCCs by various in vitro studies, including ours, it is reported to be highly context-dependent. Therefore, to delineate the precise role of Kereatin 8 phosphorylation in cancer initiation and progression, we have developed the tissue-specific transgenic mouse model expressing Keratin 8 wild type and phosphodead mutants under Keratin 14 promoter. Subjecting these mice to 7,12-dimethylbenz(a)anthracene/12-O-tetradecanoylphorbol-13-acetate-mediated skin carcinogenesis revealed that Keratin 8 phosphorylation may lead to an early onset of tumors compared to Keratin 8 wild-type expressing mice. Conclusively, the transgenic mouse model developed in the present study ascertained a positive impact of Keratin 8 phosphorylation on the neoplastic transformation of skin-squamous cells. 相似文献
100.
Nelli RK Dunham SP Kuchipudi SV White GA Baquero-Perez B Chang P Ghaemmaghami A Brookes SM Brown IH Chang KC 《Journal of virology》2012,86(17):9201-9210