全文获取类型
收费全文 | 2057篇 |
免费 | 241篇 |
国内免费 | 8篇 |
专业分类
2306篇 |
出版年
2022年 | 21篇 |
2021年 | 28篇 |
2020年 | 13篇 |
2019年 | 20篇 |
2018年 | 27篇 |
2017年 | 16篇 |
2016年 | 41篇 |
2015年 | 88篇 |
2014年 | 85篇 |
2013年 | 95篇 |
2012年 | 139篇 |
2011年 | 121篇 |
2010年 | 76篇 |
2009年 | 69篇 |
2008年 | 101篇 |
2007年 | 112篇 |
2006年 | 104篇 |
2005年 | 98篇 |
2004年 | 92篇 |
2003年 | 65篇 |
2002年 | 66篇 |
2001年 | 70篇 |
2000年 | 62篇 |
1999年 | 80篇 |
1998年 | 28篇 |
1997年 | 29篇 |
1996年 | 21篇 |
1995年 | 20篇 |
1994年 | 15篇 |
1993年 | 19篇 |
1992年 | 51篇 |
1991年 | 38篇 |
1990年 | 39篇 |
1989年 | 31篇 |
1988年 | 41篇 |
1987年 | 29篇 |
1986年 | 30篇 |
1985年 | 21篇 |
1984年 | 20篇 |
1983年 | 12篇 |
1982年 | 13篇 |
1981年 | 12篇 |
1980年 | 11篇 |
1979年 | 15篇 |
1977年 | 13篇 |
1976年 | 10篇 |
1975年 | 11篇 |
1974年 | 12篇 |
1973年 | 13篇 |
1972年 | 12篇 |
排序方式: 共有2306条查询结果,搜索用时 15 毫秒
991.
Hsieh JH Shih KY Kung HF Shiang M Lee LY Meng MH Chang CC Lin HM Shih SC Lee SY Chow TY Feng TY Kuo TT Choo KB 《Biotechnology and bioengineering》1988,32(3):334-340
We have performed controlled fed-batch fermentation experiments to compare the production level of hepatitis B surface antigen (HBsAg) by recombinant yeast Saccharomyces cerevisiae strains (YNN27/pYBH-1, YNN27/ p2mu-S11, YNN27/pDCB-S2) containing plasmid vector with alcohol dehydrogenase (ADH1), acid phosphatase (PHO5), and glyceraldehyde-3-phosphate dehydrogenase (GPD) promoter, respectively. Yeast cell concentrations of 15-35 g dry cell weight/L were obtained. By limiting phosphorous concentration, HBsAg expression level for the YNN27/p2mu-S11 strain with inducible PHO5 promoter reached 0.2-0.3 mg/L. By controlling nutrient addition rate and dissolved oxygen concentration, HBsAg concentrations of 3-10 mg/L were achieved in 60-70 h fermentation using the YNN27/pDCB-S2 strain with the constitutive GPD promoter. 相似文献
992.
The molecular basis of HbH disease in Taiwan 总被引:1,自引:0,他引:1
Hong-Wen Peng Shou-Hwa Han Teh-Yuan Chow Chao-Hung Ho King-Nien Ching Benjamin N. Chiang 《Human genetics》1988,78(2):137-139
Summary We have determined the molecular characteristics of -thalassemia in 12 HbH subjects from Taiwan by restriction endonuclease mapping with -and -specific probes. We have found four types of defects in the -thalassemia-2 genetic determinant: 3.7 type I; 4.2; CS; and T. All HbH subjects carried the ——SEA genotype in the -thalassemia-1 determinant. At least two different subtypes of ——SEA genotype were observed in this study. 相似文献
993.
The complete amino acid sequences of ribosomal proteins L17, L27, and S9 from Bacillus stearothermophilus 总被引:2,自引:0,他引:2
The complete primary structures of proteins L17, L27 and S9 extracted from the Bacillus stearothermophilus ribosomes with 1 M NaCl and purified to homogeneity by column chromatography have been determined. The amino acid sequences of these proteins are compared to those of the homologous ribosomal proteins from Escherichia coli. The number of identical amino acid residues between the homologous proteins lies between 33-55%. 相似文献
994.
Calcium dependency of pregnant rat myometrium: comparison of circular and longitudinal muscle 总被引:2,自引:0,他引:2
The purpose of this study was to determine if the changes in spontaneous contractions of circular uterine muscle during pregnancy were related to alterations in calcium (Ca) sensitivity or dependence. Circular muscle (CM) and longitudinal muscle (LM) segments from rats on Days 16-17 of gestation and at term were compared with respect to: sensitivity of potassium (K)-induced contractions to changes in extracellular Ca, and rate and magnitude of decrease of K- and acetylcholine (ACh)-induced contractions in Ca-free medium and in methoxyverapamil (D-600). The effects of low Ca and D-600 on spontaneous electrical activity of CM were also studied. Ca sensitivity was no different in CM and LM and did not change between Day 16 and term. There was no difference in the Ca-dependence of K- or ACh-induced contractions during this time. Potassium contractions declined more rapidly than ACh contractions in Ca-free media, especially in CM. Spontaneous action potentials in CM were Ca-dependent and disappeared in low Ca or D-600 on Days 16-17 and at term. Therefore the changes in contractions of CM during pregnancy are not related directly to Ca sensitivity or dependence, but indirectly via Ca modulation of the action potentials. 相似文献
995.
996.
This paper presents a two-level scheduling scheme for video transmission over downlink orthogonal frequency-division multiple access (OFDMA) networks. It aims to maximize the aggregate quality of the video users subject to the playback delay and resource constraints, by exploiting the multiuser diversity and the video characteristics. The upper level schedules the transmission of video packets among multiple users based on an overall target bit-error-rate (BER), the importance level of packet and resource consumption efficiency factor. Instead, the lower level renders unequal error protection (UEP) in terms of target BER among the scheduled packets by solving a weighted sum distortion minimization problem, where each user weight reflects the total importance level of the packets that has been scheduled for that user. Frequency-selective power is then water-filled over all the assigned subcarriers in order to leverage the potential channel coding gain. Realistic simulation results demonstrate that the proposed scheme significantly outperforms the state-of-the-art scheduling scheme by up to 6.8 dB in terms of peak-signal-to-noise-ratio (PSNR). Further test evaluates the suitability of equal power allocation which is the common assumption in the literature. 相似文献
997.
Gregory N. Dietsch Hailing Lu Yi Yang Chihiro Morishima Laura Q. Chow Mary L. Disis Robert M. Hershberg 《PloS one》2016,11(2)
VTX-2337 (USAN: motolimod) is a selective toll-like receptor 8 (TLR8) agonist, which is in clinical development as an immunotherapy for multiple oncology indications, including squamous cell carcinoma of the head and neck (SCCHN). Activation of TLR8 enhances natural killer cell activation, increases antibody-dependent cell-mediated cytotoxicity, and induces Th1 polarizing cytokines. Here, we show that VTX-2337 stimulates the release of mature IL-1β and IL-18 from monocytic cells through coordinated actions on both TLR8 and the NOD-like receptor pyrin domain containing 3 (NLRP3) inflammasome complex. In vitro, VTX-2337 primed monocytic cells to produce pro-IL-1β, pro-IL-18, and caspase-1, and also activated the NLRP3 inflammasome, thereby mediating the release of mature IL-1β family cytokines. Inhibition of caspase-1 blocked VTX-2337-mediated NLRP3 inflammasome activation, but had little impact on production of other TLR8-induced mediators such as TNFα. IL-18 activated natural killer cells and complemented other stimulatory pathways, including FcγRIII and NKG2D, resulting in IFNγ production and expression of CD107a. NLRP3 activation in vivo was confirmed by a dose-related increase in plasma IL-1β and IL-18 levels in cynomolgus monkeys administered VTX-2337. These results are highly relevant to clinical studies of combination VTX-2337/cetuximab treatment. Cetuximab, a clinically approved, epidermal growth factor receptor-specific monoclonal antibody, activates NK cells through interactions with FcγRIII and facilitates ADCC of tumor cells. Our preliminary findings from a Phase I open-label, dose-escalation, trial that enrolled 13 patients with recurrent or metastatic SCCHN show that patient NK cells become more responsive to stimulation by NKG2D or FcγRIII following VTX-2337 treatment. Together, these results indicate that TLR8 stimulation and inflammasome activation by VTX-2337 can complement FcγRIII engagement and may augment clinical responses in SCCHN patients treated with cetuximab.Trial Registration: ClinicalTrials.gov NCT01334177相似文献
998.
Jianmin?ChenEmail authorView authors OrcID profile Yanping?Chen Graham?Vail Heiman?Chow Yang?Zhang Lauren?Louie Jiali?Li Ronald?P.?Hart Mark?R.?Plummer Karl?Herrup 《Molecular neurodegeneration》2016,11(1):60
Background
Our previous studies of Alzheimer’s disease (AD) suggested that glutamine broadly improves cellular readiness to respond to stress and acts as a neuroprotectant both in vitro and in AD mouse models. We now expand our studies to a second neurodegenerative disease, ataxia-telangiectasia (A-T). Unlike AD, where clinically significant cognitive decline does not typically occur before age 65, A-T symptoms appear in early childhood and are caused exclusively by mutations in the ATM (A-T mutated) gene.Results
Genetically ATM-deficient mice and wild type littermates were maintained with or without 4 % glutamine in their drinking water for several weeks. In ATM mutants, glutamine supplementation restored serum glutamine and glucose levels and reduced body weight loss. Lost neurophysiological function assessed through the magnitude of hippocampal long term potentiation was significantly restored. Glutamine supplemented mice also showed reduced thymus pathology and, remarkably, a full one-third extension of lifespan. In vitro assays revealed that ATM-deficient cells are more sensitive to glutamine deprivation, while supra-molar glutamine (8 mM) partially rescued the reduction of BDNF expression and HDAC4 nuclear translocation of genetically mutant Atm?/? neurons. Analysis of microarray data suggested that glutamine metabolism is significantly altered in human A-T brains as well.Conclusion
Glutamine is a powerful part of an organism’s internal environment. Changes in its concentrations can have a huge impact on the function of all organ systems, especially the brain. Glutamine supplementation thus bears consideration as a therapeutic strategy for the treatment of human A-T and perhaps other neurodegenerative diseases.999.
1000.
A Chan R Shinde C C Chow C S Cockram R Swaminathan 《BMJ (Clinical research ed.)》1991,303(6810):1096-1099
OBJECTIVE--To examine whether sodium pump activity plays a part in the pathogenesis of thyrotoxic periodic paralysis. DESIGN--Measurement of platelet sodium-potassium ATPase and in vivo sodium pump activities in healthy subjects and thyrotoxic subjects with and without paralysis. SETTING--University hospital in Hong Kong. SUBJECTS--21 healthy subjects, 23 untreated thyrotoxic subjects, 13 untreated men with periodic paralysis, seven treated thyrotoxic subjects, and six treated men with periodic paralysis. MAIN OUTCOME MEASURES--Platelet Na+, K(+)-ATPase activity and plasma rubidium concentration after oral loading. RESULTS--Median (range) platelet Na+, K(+)-ATPase activity in thyrotoxic subjects was 253 (169-821) mumol inorganic phosphate/h/g protein--significantly higher than that in healthy subjects (134 (81-180) mumol/h/g protein; p less than 0.001). Na+, K(+)-ATPase activity in those with periodic paralysis was 374 (195-1196) mumol/h/g protein, again significantly higher than that in healthy subjects (p less than 0.001) and that in other thyrotoxic subjects (p less than 0.01) despite similar degrees of hyperthyroidism. Activities in treated thyrotoxic subjects with and without periodic paralysis were 148 (110-234) and 131 (86-173) mumol/h/g protein respectively. Mean (95% confidence interval) plasma rubidium concentration five hours after oral administration in thyrotoxic subjects (7.0 (6.6 to 7.5) mumol/l) was significantly lower than in healthy subjects (10.2 (9.5 to 10.9) mumol/l; p less than 0.001) and higher than in those with periodic paralysis (6.0 (5.7 to 6.3) mumol/l; p less than 0.01). CONCLUSIONS--Sodium pump activity in untreated subjects with periodic paralysis is higher than in other thyrotoxic subjects, and this may be responsible for the hypokalaemia. 相似文献