全文获取类型
收费全文 | 307篇 |
免费 | 25篇 |
专业分类
332篇 |
出版年
2022年 | 3篇 |
2021年 | 6篇 |
2019年 | 2篇 |
2018年 | 7篇 |
2017年 | 6篇 |
2016年 | 12篇 |
2015年 | 15篇 |
2014年 | 16篇 |
2013年 | 28篇 |
2012年 | 23篇 |
2011年 | 18篇 |
2010年 | 8篇 |
2009年 | 8篇 |
2008年 | 16篇 |
2007年 | 14篇 |
2006年 | 19篇 |
2005年 | 11篇 |
2004年 | 14篇 |
2003年 | 12篇 |
2002年 | 8篇 |
2001年 | 7篇 |
2000年 | 5篇 |
1999年 | 3篇 |
1998年 | 3篇 |
1997年 | 1篇 |
1996年 | 2篇 |
1995年 | 2篇 |
1994年 | 4篇 |
1993年 | 3篇 |
1992年 | 3篇 |
1991年 | 2篇 |
1989年 | 3篇 |
1988年 | 2篇 |
1987年 | 6篇 |
1985年 | 7篇 |
1984年 | 2篇 |
1983年 | 2篇 |
1982年 | 4篇 |
1980年 | 1篇 |
1978年 | 1篇 |
1977年 | 1篇 |
1976年 | 3篇 |
1975年 | 4篇 |
1974年 | 2篇 |
1973年 | 5篇 |
1972年 | 1篇 |
1971年 | 3篇 |
1969年 | 1篇 |
1968年 | 2篇 |
1965年 | 1篇 |
排序方式: 共有332条查询结果,搜索用时 0 毫秒
121.
Valiveti S Nalluri BN Hammell DC Paudel KS Stinchcomb AL 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》2004,810(2):259-267
A quantitative liquid chromatographic-electrospray ionization mass spectrometry method for the determination of naltrexone and 6beta-naltrexol in guinea pig plasma has been developed and validated using naloxone as an internal standard. A single step precipitation-extraction technique was carried out to extract the plasma samples using acetonitrile:ethyl acetate (1:1, v/v). The chromatographic separation was performed on a C(18) column using a mobile phase consisting of 35:65 (v/v) acetonitrile:2 mM ammonium acetate with 0.01 mM ammonium citrate at a flow rate of 0.25 mL/min. The analyte was detected after positive electrospray ionization using selected ion monitoring (SIM) mode. The mean recoveries for naltrexone, naltrexol, and naloxone were 91.7, 89.3, and 99.0%, respectively. The lower limit of quantification (LLOQ) for naltrexone and 6beta-naltrexol was 1.25 ng/mL, and the limit of detection (LOD) was 0.75 ng/mL. The method was applied to a pharmacokinetic study in order to assess the drug disposition of naltrexone in guinea pigs. 相似文献
122.
Pothukuchi M Nagaraja SB Kelamane S Satyanarayana S Shashidhar Babu S Dewan P Wares F 《PloS one》2011,6(7):e22500
Background
Under India''s Revised National Tuberculosis Control Programme (RNTCP), all household contacts of sputum smear positive Pulmonary Tuberculosis (PTB) patients are screened for TB. In the absence of active TB disease, household contacts aged <6 years are eligible for Isoniazid Preventive Therapy (IPT) (5 milligrams/kilogram body weight/day) for 6 months.Objectives
To estimate the number of household contacts aged <6 years, of sputum smear positive PTB patients registered for treatment under RNTCP from April to June''2008 in Krishna District, to assess the extent to which they are screened for TB disease and in its absence initiated on IPT.Methods
A cross sectional study was conducted. Households of all smear positive PTB cases (n = 848) registered for treatment from April to June''2008 were included. Data on the number of household contacts aged <6 years, the extent to which they were screened for TB disease, and the status of initiation of IPT, was collected.Results
Households of 825 (97%) patients were visited, and 172 household contacts aged <6 years were identified. Of them, 116 (67%) were evaluated for TB disease; none were found to be TB diseased and 97 (84%) contacts were initiated on IPT and 19 (16%) contacts were not initiated on IPT due to shortage of INH tablets in peripheral health centers. The reasons for non-evaluation of the remaining eligible children (n = 56, 33%) include no home visit by the health staff in 25 contacts, home visit done but not evaluated in 31 contacts. House-hold contacts in rural areas were less likely to be evaluated and initiated on IPT [risk ratio 6.65 (95% CI; 3.06–14.42)].Conclusion
Contact screening and IPT implementation under routine programmatic conditions is sub-optimal. There is an urgent need to sensitize all concerned programme staff on its importance and establishment of mechanisms for rigorous monitoring. 相似文献123.
Savitha Satyanarayana Shwetha Padmaprahlada Raghunatha Chitradurga Sarbari Bhattacharya 《Journal of biological physics》2021,47(1):79
We investigate through simulations the phenomena of magnetoreception to enable an understanding of the minimum requirements of a fail-safe mechanism, operational at the cellular level, to sense a weak magnetic field at ambient temperature in a biologically active environment. To do this, we use magnetotactic bacteria (MTB) as our model system. The magnetic field sensing ability of these bacteria is due to the presence of magnetosomes, which are internal membrane-bound organelles that contain an iron-based magnetic mineral crystal. These magnetosomes are usually found arranged in a chain aligned with the long axis of the bacterial body. This arrangement yields an overall magnetic dipole moment to the bacterial cell. To simulate this orientation process, we set up a rotational Langevin stochastic differential equation and solve it repeatedly over appropriate time steps for isolated spherical shaped MTB as well as for a more realistic model of spheroidal MTB with flagella. The orientation process appears to depend on shape parameters with spheroidal MTB showing a slower response time compared to spherical MTB. Further, our simulation also reveals that the alignment to the external magnetic field is more robust for an MTB when compared to single magnetosome. For the simulation involving magnetosomes, we include an extra torque that arises from the twisting of an attachment tether and enhance the viscosity of the surrounding medium to mimic intracellular conditions in the governing Langevin equation. The response time of alignment is found to be substantially reduced when one includes a dipole interaction term with a neighboring magnetosome and the alignment becomes less robust with increase in inter dipole distance. The alignment process can thereby be said to be very sensitively dependent on the distance between magnetosomes. Simulating the process of alignment between two neighboring magnetosomes, both in the absence and presence of an ambient magnetic field, we conclude that alignment between these dipoles at the distances typical in an MTB is highly probable and it would be the locked unit that responds to changes in the external magnetic field. 相似文献
124.
BACKGROUND: Diabetes mellitus is a chronic metabolic disorder characterized by hyperglycaemia. Increased oxidative stress and decreased antioxidant levels are the leading cause of diabetes and diabetic complications. So it is felt that supplementation of antioxidants may be useful in controlling the glucose levels and to postpone the occurrence of diabetic complications. The objective of our study is to find the influence of antioxidant supplementation (L-ascorbic acid) on tolbutamide activity in normal and diabetic rats. METHODS: L- ascorbic acid/tolbutamide/L-ascorbic acid + tolbutamide were administered orally to 3 different groups of albino rats of either sex in normal and diabetic condition. Blood samples were collected from retro-orbital puncture at different time intervals and were analyzed for blood glucose by GOD-POD method. Diabetes was induced by alloxan 100 mg/kg body weight administered by I.P route. RESULTS: L-ascorbic acid/ tolbutamide produced hypoglycaemic activity in a dose dependant manner in normal and diabetic condition. In the presence of L-ascorbic acid, tolbuatmide produced early onset of action and maintained for longer period compared to tolbutamide matching control. CONCLUSION: Supplementation of antioxidants like L-ascorbic acid was found to improve tolbutamide response in normal and diabetic rats. 相似文献
125.
Cong Y Pawlisz E Bryant P Balan S Laurine E Tommasi R Singh R Dubey S Peciak K Bird M Sivasankar A Swierkosz J Muroni M Heidelberger S Farys M Khayrzad F Edwards J Badescu G Hodgson I Heise C Somavarapu S Liddell J Powell K Zloh M Choi JW Godwin A Brocchini S 《Bioconjugate chemistry》2012,23(2):248-263
The efficacy of protein-based medicines can be compromised by their rapid clearance from the blood circulatory system. Achieving optimal pharmacokinetics is a key requirement for the successful development of safe protein-based medicines. Protein PEGylation is a clinically proven strategy to increase the circulation half-life of protein-based medicines. One limitation of PEGylation is that there are few strategies that achieve site-specific conjugation of PEG to the protein. Here, we describe the covalent conjugation of PEG site-specifically to a polyhistidine tag (His-tag) on a protein. His-tag site-specific PEGylation was achieved with a domain antibody (dAb) that had a 6-histidine His-tag on the C-terminus (dAb-His(6)) and interferon α-2a (IFN) that had an 8-histidine His-tag on the N-terminus (His(8)-IFN). The site of PEGylation at the His-tag for both dAb-His(6)-PEG and PEG-His(8)-IFN was confirmed by digestion, chromatographic, and mass-spectral studies. A methionine was also inserted directly after the N-terminal His-tag in IFN to give His(8)Met-IFN. Cyanogen bromide digestion studies of PEG-His(8)Met-IFN were also consistent with PEGylation at the His-tag. By using increased stoichiometries of the PEGylation reagent, it was possible to conjugate two separate PEG molecules to the His-tag of both the dAb and IFN proteins. Stability studies followed by in vitro evaluation confirmed that these PEGylated proteins retained their biological activity. In vivo PK studies showed that all of the His-tag PEGylated samples displayed extended circulation half-lives. Together, our results indicate that site-specific, covalent PEG conjugation at a His-tag can be achieved and biological activity maintained with therapeutically relevant proteins. 相似文献
126.
AIMS: The present investigation is aimed at assessing the suitability of cane molasses as a cheaper carbon and energy source for glucoamylase production using alginate-immobilized Thermomucor indicae-seudaticae. METHODS AND RESULTS: The culture variables for glucoamylase production were optimized by 'one-variable-at-a-time' strategy and response surface methodology (RSM). A high glucoamylase titre was attained when 40 alginate beads (c. 5x10(6) immobilized spores) were used to inoculate 50 ml of cane molasses (8%) medium in 250-ml Erlenmeyer flasks. Response surface optimization of fermentation parameters (cane molasses 7%, inoculum level 44 alginate beads per 50 ml of medium and ammonium nitrate 0.25%) resulted in 1.8-fold higher glucoamylase production (27 U ml(-1)) than that in the unoptimized medium (15 U ml(-1)). Enzyme production was also sustainable in 22 l of laboratory air-lift bioreactor. CONCLUSIONS: Cane molasses served as an excellent carbon and energy source for the economical production of glucoamylase, which was almost comparable with that in sucrose yeast-extract broth. The statistical model developed using RSM allowed determination of optimum levels of the variables for improving glucoamylase production. SIGNIFICANCE AND IMPACT OF THE STUDY: The cost of glucoamylase produced in cane molasses supplemented with ammonium nitrate was considerably lower (euro1.43 per million U) than in synthetic medium containing sucrose and yeast-extract (euro35.66 per million U). The reduction in fermentation time in air-lift bioreactor with sustainable glucoamylase titres suggested the feasibility of scale up of the process. 相似文献
127.
Amarnath Singh Ritul Kamal Mohana Krishna Reddy Mudiam Manoj Kumar Gupta Gubbala Naga Venkata Satyanarayana Vipin Bihari Nishi Shukla Altaf Hussain Khan Chandrasekharan Nair Kesavachandran 《PloS one》2016,11(2)
Indoor air quality and heat exposure have become an important occupational health and safety concern in several workplaces including kitchens of hotels. This study investigated the heat, particulate matter (PM), total volatile organic compounds (TVOCs) and polycyclic aromatic hydrocarbons (PAHs) emissions in indoor air of commercial kitchen and its association with kidney dysfunctions among kitchen workers. A cross sectional study was conducted on 94 kitchen workers employed at commercial kitchen in Lucknow city, North India. A questionnaire-based survey was conducted to collect the personal and occupational history of the kitchen workers. The urine analysis for specific gravity and microalbuminuria was conducted among the study subjects. Indoor air temperature, humidity, wet/ dry bulb temperature and humidex heat stress was monitored during cooking activities at the kitchen. Particulate matter (PM) for 1 and 2.5 microns were monitored in kitchen during working hours using Hazdust. PAHS in indoor air was analysed using UHPLC. Urinary hydroxy-PAHs in kitchen workers were measured using GC/MS-MS. Higher indoor air temperature, relative humidity, PM1 and PM2.5 (p<0.001) was observed in the kitchen due to cooking process. Indoor air PAHs identified are Napthalene, fluorine, acenaphthene, phenanthrene, pyrene, chrysene and indeno [1,2,3-cd) pyrene. Concentrations of all PAHs identified in kitchen were above the permissible OSHA norms for indoor air. Specific gravity of urine was significantly higher among the kitchen workers (p<0.001) as compared to the control group. Also, the prevalence of microalbuminuria was higher (p<0.001) among kitchen workers. Urinary PAH metabolites detected among kitchen workers were 1-NAP, 9-HF, 3-HF, 9-PHN and 1-OHP. Continuous heat exposure in kitchens due to cooking can alter kidney functions viz., high specific gravity of urine in kitchen workers. Exposure to PM, VOCs and PAHs in indoor air and presence of urinary PAHs metabolites may lead to inflammation, which can cause microalbuminuria in kitchen workers, as observed in the present study. 相似文献
128.
129.
Sanjeev R. Patil Satyanarayana Bollikonda Rajendra H. Patil Jaiprakash N. Sangshetti Anil S. Bobade Ashish Asrondkar Padi Pratap Reddy Devanand B. Shinde 《Bioorganic & medicinal chemistry letters》2018,28(3):482-487
A series of 5-substitutedbenzylideneamino-2-butylbenzofuran-3-yl-4-methoxyphenyl methanones is synthesized and evaluated for antileishmanial and antioxidant activities. Compounds 4f (IC50?=?52.0?±?0.09?µg/ml), 4h (IC50?=?56.0?±?0.71?µg/ml) and 4l (IC50?=?59.3?±?0.55?µg/ml) were shown significant antileishmanial when compared with standard sodium stibogluconate (IC50?=?490.0?±?1.5?µg/ml). Antioxidant study revealed that compounds 4i (IC50?=?2.44?±?0.47?µg/ml) and 4l (IC50?=?3.69?±?0.44?µg/ml) have shown potent comparable activity when compared with standard ascorbic acid (IC50?=?3.31?±?0.34?µg/ml). Molecular docking study was carried out which replicating results of biological activity in case of initial hits 4f and 4h suggesting that these compounds have a potential to become lead molecules in drug discovery process. In silico ADME study was performed for predicting pharmacokinetic profile of the synthesised antileishmanial agents and expressed good oral drug like behaviour. 相似文献
130.