全文获取类型
收费全文 | 2866篇 |
免费 | 250篇 |
国内免费 | 8篇 |
专业分类
3124篇 |
出版年
2022年 | 29篇 |
2021年 | 47篇 |
2020年 | 24篇 |
2019年 | 31篇 |
2018年 | 44篇 |
2017年 | 24篇 |
2016年 | 54篇 |
2015年 | 122篇 |
2014年 | 126篇 |
2013年 | 146篇 |
2012年 | 199篇 |
2011年 | 201篇 |
2010年 | 109篇 |
2009年 | 102篇 |
2008年 | 142篇 |
2007年 | 136篇 |
2006年 | 157篇 |
2005年 | 150篇 |
2004年 | 141篇 |
2003年 | 109篇 |
2002年 | 82篇 |
2001年 | 85篇 |
2000年 | 84篇 |
1999年 | 68篇 |
1998年 | 42篇 |
1997年 | 30篇 |
1996年 | 24篇 |
1995年 | 23篇 |
1994年 | 22篇 |
1993年 | 18篇 |
1992年 | 58篇 |
1991年 | 36篇 |
1990年 | 38篇 |
1989年 | 43篇 |
1988年 | 29篇 |
1987年 | 29篇 |
1986年 | 32篇 |
1985年 | 35篇 |
1984年 | 20篇 |
1983年 | 30篇 |
1982年 | 15篇 |
1981年 | 13篇 |
1979年 | 21篇 |
1978年 | 10篇 |
1977年 | 21篇 |
1976年 | 14篇 |
1975年 | 11篇 |
1974年 | 10篇 |
1972年 | 23篇 |
1971年 | 17篇 |
排序方式: 共有3124条查询结果,搜索用时 0 毫秒
991.
Po-Cheng Chang Hung-Ta Wo Hui-Ling Lee Shien-Fong Lin Ming-Shien Wen Yen Chu San-Jou Yeh Chung-Chuan Chou 《PloS one》2015,10(4)
Background
L-type calcium current reactivation plays an important role in development of early afterdepolarizations (EADs) and torsades de pointes (TdP). Secondary intracellular calcium (Cai) rise is associated with initiation of EADs.Objective
To test whether inhibition of sarcoplasmic reticulum (SR) Ca2+ cycling suppresses secondary Cai rise and genesis of EADs.Methods
Langendorff perfusion and dual voltage and Cai optical mapping were conducted in 10 rabbit hearts. Atrioventricular block (AVB) was created by radiofrequency ablation. After baseline studies, E4031, SR Ca2+ cycling inhibitors (ryanodine plus thapsigargin) and nifedipine were then administrated subsequently, and the protocols were repeated.Results
At baseline, there was no spontaneous or pacing-induced TdP. After E4031 administration, action potential duration (APD) was significantly prolonged and the amplitude of secondary Cai rise was enhanced, and 7 (70%) rabbits developed spontaneous or pacing-induced TdP. In the presence of ryanodine plus thapsigargin, TdP inducibility was significantly reduced (2 hearts, 20%, p = 0.03). Although APD was significantly prolonged (from 298 ± 30 ms to 457 ± 75 ms at pacing cycle length of 1000 m, p = 0.007) by ryanodine plus thapsigargin, the secondary Cai rise was suppressed (from 8.8 ± 2.6% to 1.2 ± 0.9%, p = 0.02). Nifedipine inhibited TdP inducibility in all rabbit hearts.Conclusion
In this AVB and long QT rabbit model, inhibition of SR Ca2+ cycyling reduces the inducibility of TdP. The mechanism might be suppression of secondary Cai rise and genesis of EADs. 相似文献992.
Melina Messaoudi Milen Milenkov Werner C. Albrich Mark P. G. van der Linden Thomas Bénet Monidarin Chou Mariam Sylla Patricia Barreto Costa Nathalie Richard Keith P. Klugman Hubert P. Endtz Gláucia Paranhos-Baccalà Jean-No?l Telles 《PloS one》2016,11(3)
For epidemiological and surveillance purposes, it is relevant to monitor the distribution and dynamics of Streptococcus pneumoniae serotypes. Conventional serotyping methods do not provide rapid or quantitative information on serotype loads. Quantitative serotyping may enable prediction of the invasiveness of a specific serotype compared to other serotypes carried. Here, we describe a novel, rapid multiplex real-time PCR assay for identification and quantification of the 40 most prevalent pneumococcal serotypes and the assay impacts in pneumonia specimens from emerging and developing countries. Eleven multiplex PCR to detect 40 serotypes or serogroups were optimized. Quantification was enabled by reference to standard dilutions of known bacterial load. Performance of the assay was evaluated to specifically type and quantify S. pneumoniae in nasopharyngeal and blood samples from adult and pediatric patients hospitalized with pneumonia (n = 664) from five different countries. Serogroup 6 was widely represented in nasopharyngeal specimens from all five cohorts. The most frequent serotypes in the French, South African, and Brazilian cohorts were 1 and 7A/F, 3 and 19F, and 14, respectively. When both samples were available, the serotype in blood was always present as carriage with other serotypes in the nasopharynx. Moreover, the ability of a serotype to invade the bloodstream may be linked to its nasopharyngeal load. The mean nasopharyngeal concentration of the serotypes that moved to the blood was 3 log-fold higher than the ones only found in the nasopharynx. This novel, rapid, quantitative assay may potentially predict some of the S. pneumoniae serotypes invasiveness and assessment of pneumococcal serotype distribution. 相似文献
993.
Low-frequency vibrations of DNA molecules. 总被引:1,自引:0,他引:1
K C Chou 《The Biochemical journal》1984,221(1):27-31
A model for calculating the low-frequency modes in DNA molecules is presented. The present model is associated with the 'breathing' of a DNA molecule as well as its complementary hydrogen bonds. The calculated results show excellent agreement with the observed low-frequency wavenumber (30 cm-1). Consequently, such an internal motion as reflected in the proposed model might be the origin of the observed low-frequency vibration in DNA molecules. This is helpful for investigating the relevant biological functions, which so far have been discussed by many scientists. 相似文献
994.
Summary We have cultivated a hybridoma cell-line H505AC in suspension and alginate immobilized cell bioreactors to produce anti-Hepatitis B surface Antigen (anti-HBsAg) monoclonal antibody IgM. The specific IgM production rates correlate linearly with the specific glucose consumption rate in suspension culture with a maximum production rate of 300 g/106 cells/day. In alginate-cell immobilized airlift bioreactor, a total of 1143 milligrams IgM was produced in 9 days operation with a volumetric productivity 44.1 mg/day.L 相似文献
995.
An approach to the design of electrodes for the production of sensors, which show significant changes to the passage of current in response to the concentration of target protein molecules, is presented. Screen-printed platinum electrodes, modified with two separately applied conducting polymer layers, have been developed as a potential route to forming cheap disposable protein sensors. To achieve a heightened response for the target molecules, an initial layer of polypyrrole was formed on the electrode's surface by electro-deposition. This composite was then employed as a substrate for the subsequent electro-deposition of a relatively thin 'sensing layer' of poly-aminophenylboronic acid. Cyclic voltammetry (CV) of the prepared films revealed an excursion in the current versus potential curve in the anodic phase at approximately 0.0 to +0.2V. It was clearly shown that the introduction of proteins into the CV cell resulted in a measurable decrease in the passage of current in buffered aqueous media. Measured current reductions observed on introducing lysozyme (10ppm) into the test solution were 2.3x10(-6)A for an electrode formed with a poly-aminophenylboronic acid layer on platinum, and 1.75x10(-5)A for a composite electrode formed with poly-aminophenylboronic acid on a polypyrrole coated platinum substrate. The introduction of the competing analytes, dl adrenaline or dopamine, at concentrations typically found in human urine, had little effect on the sensor's response. Additionally, the sensing system was able to maintain a response to added target proteins with as much as 2vol.% urine in the test solution. Using the electrodes in high concentrations of competing physiological analytes, they were able to respond to protein concentrations as low as 0.5ppm in buffered solutions containing urea at a concentration representative of human urine (17,000ppm), which additionally contained glucose (1000ppm). 相似文献
996.
A voltage-activated inward-rectifying K+ conductance (lKi) appears in human promyelocytic leukemia (HL-60) cells during phorbol ester-induced differentiation into macrophages. This conductance was detected in the cells 24 hours after exposure to phorbol-12-myristate-13-acetate (PMA), as the cells began to express the macrophage phenotype, and continued to increase for 4 days after PMA exposure. The magnitude of inward current was a function of external K+; current was blocked by extracellular or intracellular Cs+ and by extracellular Ba++. Hyperpolarization produced activation at membrane potentials more negative than -80 mV, and a slower, partial inactivation also occurred at potentials more negative than -100 mV. This conductance was not detected in proliferating cells nor in granulocytes derived from HL-60 cells which were induced to differentiate with retinoic acid (RA). Exposure of differentiated macrophages to recombinant human CSF-1 produced inhibition of the lKi beginning within 1 minute after exposure. CSF-1 inhibition of lKi channels in cell-attached patches indicated that channel modulation was via intracellular mediators. The rapid inhibition of the inward rectifier by the macrophage-specific CSF-1 appears to be one of the earliest cellular responses to this factor. 相似文献
997.
Shu-Qing Wang Qi-Shi Du Ri-Bo Huang Da-Wei Zhang Kuo-Chen Chou 《Biochemical and biophysical research communications》2009,386(3):432-436
The neuraminidase (NA) of influenza virus is the target of anti-flu drugs oseltamivir and zanamivir. Clinical practices showed that oseltamivir was effective to treat the 2009-H1N1 influenza but failed to the 2006-H5N1 avian influenza. To perform an in-depth analysis on such a drug-resistance problem, the 2009-H1N1-NA structure was developed. To compare it with the crystal 2006-H5N1-NA structure as well as the 1918 influenza virus H1N1-NA structure, the multiple sequential and structural alignments were performed. It has been revealed that the hydrophobic residue Try347 in H5N1-NA does not match with the hydrophilic carboxyl group of oseltamivir as in the case of H1N1-NA. This may be the reason why H5N1 avian influenza virus is drug-resistant to oseltamivir. The finding provides useful insights for how to modify the existing drugs, such as oseltamivir and zanamivir, making them not only become more effective against H1N1 virus but also effective against H5N1 virus. 相似文献
998.
Yu-Tze Horng Kai-Chih Chang Ta-Chung Chou Chung-Jen Yu Chih-Ching Chien Yu-Hong Wei Po-Chi Soo 《Journal of industrial microbiology & biotechnology》2010,37(7):707-716
1,3-Propanediol (1,3-PD) can be used for the industrial synthesis of a variety of compounds, including polyesters, polyethers,
and polyurethanes. 1,3-PD is generated from petrochemical and microbial sources. 1,3-Propanediol is a typical product of glycerol
fermentation, while acetate, lactate, 2,3-butanediol, and ethanol also accumulate during the process. Substrate and product
inhibition limit the final concentration of 1,3-propanediol in the fermentation broth. It is impossible to increase the yield
of 1,3-propanediol by using the traditional whole-cell fermentation process. In this study, dhaD and dhaK, the genes for glycerol dehydrogenase and dihydroxyacetone kinase, respectively, were inactivated by homologous recombination
in Klebsiella pneumoniae. The dhaD/dhaK double mutant (designated TC100), selected from 5,000 single or double cross homologous recombination mutants, was confirmed
as a double cross by using polymerase chain reaction. Analysis of the cell-free supernatant with high-performance liquid chromatography
revealed elimination of lactate and 2,3-butanediol, as well as ethanol accumulation in TC100, compared with the wild-type
strain. Furthermore, 1,3-propanediol productivity was increased in the TC100 strain expressing glycerol dehydratase and 1,3-PDO
dehydrogenase regulated by the arabinose PBAD promoter. The genetic engineering and medium formulation approaches used here should aid in the separation of 1,3-propanediol
from lactate, 2,3-butanediol, and ethanol and lead to increased production of 1,3-propanediol in Klebsiella pneumoniae. 相似文献
999.
1000.