全文获取类型
收费全文 | 196篇 |
免费 | 12篇 |
国内免费 | 1篇 |
出版年
2023年 | 1篇 |
2022年 | 2篇 |
2021年 | 7篇 |
2020年 | 4篇 |
2019年 | 4篇 |
2018年 | 2篇 |
2017年 | 4篇 |
2016年 | 8篇 |
2015年 | 8篇 |
2014年 | 14篇 |
2013年 | 14篇 |
2012年 | 16篇 |
2011年 | 11篇 |
2010年 | 14篇 |
2009年 | 12篇 |
2008年 | 6篇 |
2007年 | 8篇 |
2006年 | 4篇 |
2005年 | 4篇 |
2004年 | 4篇 |
2003年 | 5篇 |
2002年 | 2篇 |
2001年 | 4篇 |
2000年 | 4篇 |
1999年 | 8篇 |
1998年 | 11篇 |
1997年 | 4篇 |
1996年 | 3篇 |
1995年 | 1篇 |
1994年 | 3篇 |
1993年 | 1篇 |
1992年 | 2篇 |
1991年 | 2篇 |
1990年 | 1篇 |
1988年 | 2篇 |
1987年 | 1篇 |
1986年 | 1篇 |
1985年 | 2篇 |
1983年 | 3篇 |
1982年 | 1篇 |
1975年 | 1篇 |
排序方式: 共有209条查询结果,搜索用时 31 毫秒
31.
Margriet A. van Gestel Arjen J. Boender Veronne A. J. de Vrind Keith M. Garner Mieneke C. M. Luijendijk Roger A. H. Adan 《PloS one》2014,9(5)
To promote the efficient and safe application of adeno-associated virus (AAV) vectors as a gene transfer tool in the central nervous system (CNS), transduction efficiency and clearance were studied for serotypes commonly used to transfect distinct areas of the brain. As AAV2 was shown to transduce only small volumes in several brain regions, this study compares the transduction efficiency of three AAV pseudotyped vectors, namely AAV2/1, AAV2/5 and AAV2/8, in the ventromedial nucleus of the hypothalamus (VMH). No difference was found between AAV2/1 and AAV2/5 in transduction efficiency. Both AAV2/1 and AAV2/5 achieved a higher transduction rate than AAV2/8. One hour after virus administration to the brain, no viral particles could be traced in blood, indicating that no or negligible numbers of virions crossed the blood-brain barrier. In order to investigate survival of AAV in blood, clearance was determined following systemic AAV administration. The half-life of AAV2/1, AAV2/2, AAV2/5 and AAV2/8 was calculated by determining virus clearance rates from blood after systemic injection. The half-life of AAV2/2 was 4.2 minutes, which was significantly lower than the half-lives of AAV2/1, AAV2/5 and AAV2/8. With a half-life of more than 11 hours, AAV2/8 particles remained detectable in blood significantly longer than AAV2/5. We conclude that application of AAV in the CNS is relatively safe as no AAV particles are detectable in blood after injection into the brain. With a half-life of 1.67 hours of AAV2/5, a systemic injection with 1×109 genomic copies of AAV would be fully cleared from blood after 2 days. 相似文献
32.
Conformation of the core sequence in melanocortin peptides directs selectivity for the melanocortin MC3 and MC4 receptors. 总被引:2,自引:0,他引:2
J Oosterom W A Nijenhuis W M Schaaper J Slootstra R H Meloen W H Gispen J P Burbach R A Adan 《The Journal of biological chemistry》1999,274(24):16853-16860
Melanocortin peptides regulate a variety of physiological processes. Five melanocortin receptors (MC-R) have been cloned and the MC3R and MC4R are the main brain MC receptors. The aim of this study was to identify structural requirements in both ligand and receptor that determine gamma-melanocyte-stimulating hormone (MSH) selectivity for the MC3R versus the MC4R. Substitution of Asp10 in [Nle4]Lys-gamma2-MSH for Gly10 from [Nle4]alpha-MSH, increased both activity and affinity for the MC4R while the MC3R remained unaffected. Analysis of chimeric MC3R/MC4Rs and mutant MC4Rs showed that Tyr268 of the MC4R mainly determined the low affinity for [Nle4]Lys-gamma2-MSH. The data demonstrate that Asp10 determines selectivity for the MC3R, however, not through direct side chain interactions, but probably by influencing how the melanocortin core sequence is presented to the receptor-binding pocket. This is supported by mutagenesis of Tyr268 to Ile in the MC4R which increased affinity and activity for [Nle4]Lys-gamma2-MSH, but decreased affinity for two peptides with constrained cyclic structure of the melanocortin core sequence, MT-II and [D-Tyr4]MT-II, that also displayed lower affinity for the MC3R. This study provides a general concept for peptide receptor selectivity, in which the major determinant for a selective receptor interaction is the conformational presentation of the core sequence in related peptides to the receptor-binding pocket. 相似文献
33.
Lucas R Lopes Vitor AR Miranda Rodrigo A Goes Gabriel GA Souza Giuliana R Souza Jessica CS Rocha Victor RA Cossich Jamila A Perini 《Biology of sport / Institute of Sport》2021,38(4):703
The COVID-19 pandemic has presented significant challenges and implications for the sports community. Thus, this study aimed to describe the prevalence of COVID-19 in Brazilian athletes and identify the epidemiological, clinical, athletic, life and health factors associated with the disease in these individuals. A cross-sectional study was performed involving 414 athletes from 22 different sports using an online questionnaire from August to November 2020. The association between the athletes’ characteristics and COVID-19 was evaluated using a logistic regression model. The prevalence of COVID-19 was 8.5%, although only 40% of athletes reported having been tested. Being under 27 years of age (3-fold), having children (~5-fold), having a teammate test positive for COVID-19 (2.5-fold), and smoking (14-fold) were associated with a possible higher risk of disease. Almost 20% of athletes self-reported musculoskeletal injuries during the period of the pandemic that was studied. Athletes with a university education (P = 0.02), a profession other than sports (P < 0.001), those from a low-income family (P = 0.01), and public health system users (P = 0.04) were significantly less frequently tested for COVID-19, whereas international competitors, athletes who received a wage, and athletes who had a teammate who tested positive for COVID-19 were 2-, 3-, and 15-fold more likely to be tested for COVID-19, respectively. Approximately 26% of the athletes who tested negative or were untested reported more than three characteristic COVID-19 symptoms, and 11% of athletes who tested positive for COVID-19 were asymptomatic. The identification of modifiable (have children, smoking, and teammates positively tested) and non-modifiable (age under 27 years) factors related to COVID-19 in athletes can contribute to implementing surveillance programmes to decrease the incidence of COVID-19 in athletes and its negative impacts in sports. 相似文献
34.
Federico Antonio Gutiérrez Miceli Adan Domínguez Estudillo Miguel Abud Archila Teresa del Rosario Ayora Talavera Luc Dendooven 《In vitro cellular & developmental biology. Plant》2008,44(1):33-39
Renealmia mexicana (Klotzsch ex. Petersen) is a tropical plant found in southern México with an ornamental value and a potential source of curcuminoids.
Its distribution in Chiapas has decreased because of deforestation and low propagation and germination rate, so a protocol
for in vitro propagation was developed. An orthogonal experimental design of L9 (34) in triplicate was used to investigate the effect of 6-benzyl adenine (BA), indole butyric acid (IBA), silver nitrate (AgNO3), and sucrose on shoot, root, and leaf development of plantlets grown in vitro. Plantlets with well-developed shoots and roots were transferred to pots containing a mixture of peat moss and agrolite for
hardening before transfer to soil. The Murashige and Skoog (Physiol. Plant. 15:473–497, 1962) mineral medium (MS) supplemented
with 4.4 μM BA, 2.5 μM IBA, 11.7 μM AgNO3y and 5.5% (w/v) sucrose gave most shoots, 8.9 μM BA, 2.5 μM IBA, 17.7 μM AgNO3 and 5.5% (w/v) sucrose most roots, and 8.9 μM BA, 4.9 μM IBA, 11.7 μM AgNO3 and 3.0% (w/v) sucrose most leaves, although other combinations were statistically equivalent in each case. Sucrose was the factor that
most explained the variation in the promotion of shoots, roots, and leaves. The protocol developed resulted in up to 100%
survival when plantlets were transferred to soil using AgNO3, confirming that hardening of plantlets in vitro using hormonal stimulation was a suitable strategy to improve acclimatization. 相似文献
35.
JF Yuan SJ Zhang O Jafer RA Furlong OE Chausiaux CA Sargent GH Zhang NA Affara 《BMC microbiology》2009,9(1):246
Background
Pseudorabies virus (PRV) is an alphaherpesviruses whose native host is pig. PRV infection mainly causes signs of central nervous system disorder in young pigs, and respiratory system diseases in the adult. 相似文献36.
华南丘陵地区农林复合生态系统晚稻田甲烷和氧化亚氮排放 总被引:5,自引:0,他引:5
采用静态箱-气相色谱法对晚稻田甲烷(CH4)和氧化亚氮(N2O)排放进行田间原位测定。结果表明,有植株参与的稻田CH4排放通量季节变化与地下5cm温度呈显著正相关关系。稻田CH4和N2O季节平均排放通量在有植株参与时分别为1.16±0.38mgm-2h-1和42.33±20.00μgm-2h-1,而无植株参与的分别为0.15±0.11mgm-2h-1和51.69±15.87μgm-2h-1。水稻种植对CH4的排放影响较大,对N2O的排放影响较小,有植株参与的稻田CH4平均排放量显著高于无植株参与的稻田,N2O的平均排放量无显著差异。 相似文献
37.
Frederico?Pieruccini-Faria Kaylena?A?Ehgoetz Martens Carolina?RA?Silveira Jeffery?A?Jones Quincy?J?AlmeidaEmail author 《BMC neurology》2014,14(1):250
Background
Recent research has argued that removal of relevant sensory information during the planning and control of simple, self-paced walking can result in increased demand on central processing resources in Parkinson’s disease (PD). However, little is known about more complex gait tasks that require planning of gait adaptations to cross over an obstacle in PD.Methods
In order to understand the interaction between availability of visual information relevant for self-motion and cognitive load, the current study evaluated PD participants and healthy controls while walking toward and stepping over an obstacle in three visual feedback conditions: (i) no visual restrictions; (ii) vision of the obstacle and their lower limbs while in complete darkness; (iii) vision of the obstacle only while in complete darkness; as well as two conditions including a cognitive load (with a dual task versus without a dual task). Each walk trial was divided into an early and late phase to examine changes associated with planning of step adjustments when approaching the obstacle.Results
Interactions between visual feedback and dual task conditions during the obstacle approach were not significant. Patients with PD had greater deceleration and step time variability in the late phase of the obstacle approach phase while walking in both dark conditions compared to control participants. Additionally, participants with PD had a greater number of obstacle contacts when vision of their lower limbs was not available specifically during the dual task condition. Dual task performance was worse in PD compared to healthy control participants, but notably only while walking in the dark regardless of visual feedback.Conclusions
These results suggest that reducing visual feedback while approaching an obstacle shifts processing to somatosensory feedback to guide movement which imposes a greater demand on planning resources. These results are key to fully understanding why trips and falls occur in those with PD.38.
Heather A Huet Joseph D Growney Jennifer A Johnson Jing Li Sanela Bilic Lance Ostrom Mohammad Zafari Colleen Kowal Guizhi Yang Axelle Royo Michael Jensen Bruno Dombrecht Kris RA Meerschaert Joost A Kolkman Karen D Cromie Rebecca Mosher Hui Gao Alwin Schuller Randi Isaacs William R Sellers Seth A Ettenberg 《MABS-AUSTIN》2014,6(6):1560-1570
Multiple therapeutic agonists of death receptor 5 (DR5) have been developed and are under clinical evaluation. Although these agonists demonstrate significant anti-tumor activity in preclinical models, the clinical efficacy in human cancer patients has been notably disappointing. One possible explanation might be that the current classes of therapeutic molecules are not sufficiently potent to elicit significant response in patients, particularly for dimeric antibody agonists that require secondary cross-linking via Fcγ receptors expressed on immune cells to achieve optimal clustering of DR5. To overcome this limitation, a novel multivalent Nanobody approach was taken with the goal of generating a significantly more potent DR5 agonist. In the present study, we show that trivalent DR5 targeting Nanobodies mimic the activity of natural ligand, and furthermore, increasing the valency of domains to tetramer and pentamer markedly increased potency of cell killing on tumor cells, with pentamers being more potent than tetramers in vitro. Increased potency was attributed to faster kinetics of death-inducing signaling complex assembly and caspase-8 and caspase-3 activation. In vivo, multivalent Nanobody molecules elicited superior anti-tumor activity compared to a conventional DR5 agonist antibody, including the ability to induce tumor regression in an insensitive patient-derived primary pancreatic tumor model. Furthermore, complete responses to Nanobody treatment were obtained in up to 50% of patient-derived primary pancreatic and colon tumor models, suggesting that multivalent DR5 Nanobodies may represent a significant new therapeutic modality for targeting death receptor signaling. 相似文献
39.
On autocorrelation in a Poisson regression model 总被引:3,自引:0,他引:3
40.
J. E. Friedman P. I. Lelkes E. Lavie K. Rosenheek F. Schneeweiss RA. S. Schneider† 《Journal of neurochemistry》1985,44(5):1391-1402
Changes in plasma membrane potential of isolated bovine adrenal chromaffin cells were measured independently by two chemical probe methods and related to corresponding effects on catecholamine secretion. The lipophilic cation tetraphenylphosphonium (TPP+) and the carbocyanine dye 3,3'-dipropylthiadicarbocyanine [DiS-C3-(5)] were used. The necessity of evaluating the subcellular distribution of TPP+ among cytoplasmic, mitochondrial, secretory granule, and bound compartments was demonstrated and the resting plasma membrane potential determined to be -55 mV. The relationship between membrane potential and catecholamine secretion was determined in response to variations in extracellular K+ and to the presence of several secretagogues including cholinergic receptor ligands, veratridine, and ionophores for Na+ and K+. The dependence of potential on K+ concentration fit the Goldman constant field equation with a Na/K permeability ratio of 0.1. The dependence of both K+- and veratridine-evoked catecholamine secretion on membrane potential exhibited a potential threshold of about -40 mV before a significant rise in secretion occurred. This is likely related to the threshold for opening of voltage-sensitive Ca2+ channels. Acetylcholine and nicotine evoked a large secretory response without a sufficiently sustained depolarization to be detectable by the relatively slow potential sensitive chemical probes. Decamethonium induced a detectable depolarization of the chromaffin cells. Veratridine and gramicidin evoked both membrane depolarization and catecholamine release. By contrast the K ionophore valinomycin evoked significant levels of secretion without any depolarization. This is consistent with its utilization of an intracellular source of Ca2+ and the independence of its measured secretory response on extracellular Ca2+. 相似文献