全文获取类型
收费全文 | 252篇 |
免费 | 5篇 |
国内免费 | 55篇 |
出版年
2023年 | 1篇 |
2022年 | 3篇 |
2021年 | 6篇 |
2020年 | 5篇 |
2019年 | 6篇 |
2018年 | 2篇 |
2017年 | 1篇 |
2016年 | 11篇 |
2015年 | 7篇 |
2014年 | 8篇 |
2013年 | 16篇 |
2012年 | 35篇 |
2011年 | 38篇 |
2010年 | 17篇 |
2009年 | 22篇 |
2008年 | 33篇 |
2007年 | 17篇 |
2006年 | 10篇 |
2005年 | 20篇 |
2004年 | 13篇 |
2003年 | 7篇 |
2002年 | 10篇 |
2001年 | 4篇 |
1999年 | 2篇 |
1998年 | 2篇 |
1997年 | 3篇 |
1996年 | 3篇 |
1995年 | 4篇 |
1994年 | 1篇 |
1993年 | 3篇 |
1991年 | 1篇 |
1986年 | 1篇 |
排序方式: 共有312条查询结果,搜索用时 15 毫秒
31.
Internalization and recycling of G protein-coupled receptors (GPCRs), such as the mu-opioid receptor, largely depend on agonist stimulation. Agonist-promoted internalization of some GPCRs has been shown to mediate receptor desensitization, resensitization, and down-regulation. In this study, we investigated whether different mu opioid agonists displayed different effects in receptor internalization and recycling, the potential mechanisms involved in ohmefentanyl-induced internalization process. In transfected Sf9 insect cells expressing 6His-tagged wild type mu opioid receptor, exposure to 100 nM ohmefentanyl caused a maximum internalization of the receptor at 30 min and receptors seemed to reappear at the cell membrane after 60 min as determined by radioligand binding assay. Ohmefentanyl-induced human mu opioid receptor internalization was concentration-dependent, with about 40% of the receptors internalized following a 30-min exposure to 1 microM ohmefentanyl. 10 microM morphine and 1 microM DAMGO could also induce about 40% internalization. The antagonist naloxone and pretreatment with pertussis toxin both blocked ohmefentanyl-induced internalization without affecting internalization themselves. Incubation with sucrose 0.45 M significantly inhibited ohmefentanyl-induced internalization of the mu receptor. The removal of agonists ohmefentanyl and morphine resulted in the receptors gradually returning to the cell surface over a 60 min period, while the removal of agonist DAMGO only partly resulted in the receptor recycling. The results of this study suggest that ohmefentanyl-induced internalization of human mu opioid receptor in Sf9 insect cells occurs via Gi/o protein-dependent process that likely involves clathrin-coated pits. In addition, the recycling process displays the differential modes of action of different agonists. 相似文献
32.
Green RB Hatini V Johansen KA Liu XJ Lengyel JA 《Development (Cambridge, England)》2002,129(15):3645-3656
Elongation of the Drosophila embryonic hindgut epithelium occurs by a process of oriented cell rearrangement requiring the genes drumstick (drm) and lines (lin). The elongating hindgut becomes subdivided into domains -- small intestine, large intestine and rectum -- each characterized by a specific pattern of gene expression dependent upon normal drm and lin function. We show that drm encodes an 81 amino acid (10 kDa) zinc finger protein that is a member of the Odd-skipped family. drm expression is localized to the developing midgut-hindgut junction and is required to establish the small intestine, while lin is broadly expressed throughout the gut primordium and represses small intestine fate. lin is epistatic to drm, suggesting a model in which localized expression of drm blocks lin activity, thereby allowing small intestine fate to be established. Further supporting this model, ectopic expression of Drm throughout the hindgut produces a lin phenotype. Biochemical and genetic data indicate that the first conserved zinc finger of Drm is essential for its function. We have thus defined a pathway in which a spatially localized zinc finger protein antagonizes a globally expressed protein, thereby leading to specification of a domain (the small intestine) necessary for oriented cell rearrangement. 相似文献
33.
Shi-Zhu Bian Jun Jin Ji-Hang Zhang Qian-Ning Li Jie Yu Shi-Yong Yu Jian-Fei Chen Xue-Jun Yu Jun Qin Lan Huang 《PloS one》2015,10(11)
Objective
We aimed to describe the heterogeneity in the clinical presentation of acute mountain sickness (AMS) and to identify its primary risk factors.Methods
The participants (n = 163) received case report form questionnaires, and their heart rate (HR), oxygen saturation (SpO2), echocardiographic and transcranial Doppler variables, ability to perform mental and physical work, mood and psychological factors were assessed within 18 to 22 hours after arriving at 3700 m from sea level (500 m) by plane. First, we examined the differences in all variables between the AMS-positive and the AMS-negative groups. Second, an adjusted regression analysis was performed after correlation and principal component analyses.Results
The AMS patients had a higher diastolic vertebral artery velocity (Vd; p = 0.018), a higher HR (p = 0.006) and a lower SpO2. The AMS subjects also experienced poorer sleep quality, as quantified using the Athens Insomnia Scale (AIS). Moreover, the AMS population exhibited more negative mood states, including anxiety, depression, hostility, fatigue and confusion. Five principal components focused on diverse aspects were also found to be significant. Additionally, more advanced age (p = 0.007), a higher HR (p = 0.034), a higher Vd (p = 0.014), a higher AIS score (p = 0.030), a decreased pursuit aiming capacity (p = 0.035) and decreased vigor (p = 0.015) were risk factors for AMS.Conclusions
Mood states play critical roles in the development of AMS. Furthermore, an elevated HR and Vd, advanced age, elevated AIS sores, insufficient vigor and decreased mental work capacity are independent risk factors for AMS. 相似文献34.
Li-Qiong Cai Zai-Xing Wang Wen-Sheng Lu Jian-Wen Han Liang-Dan Sun Wen-Hui Du Shu-Mei Zhang Xian-Bo Zuo Xue-Jun Zhang Sen Yang 《Molecular biology reports》2010,37(1):389-394
Systemic lupus erythematosus (SLE) is a complex systemic disease influenced by genetic and environmental factors. The exact
pathogenesis of SLE is still unknown. Recently, several genome-wide association studies (GWA) in European population have
found many novel susceptibility genes for SLE including TNFAIP3. In order to examine whether TNFAIP3 is associated with SLE
in Chinese Han population, we genotyped one of its non-synonymous mutation SNP rs2230926, showing significant association
evidence with SLE in European population, with 1,420 cases and 4,461 controls of Chinese Han by using Sequenom MassArray system.
Highly significant association between SNP rs2230926 and SLE of Chinese Han was detected [OR = 1.65, 95% confidence interval
(CI): 1.392–1.986, P = 2.03 × 10−8]. Interestingly, rs2230926 of TNFAIP3 was also associated with arthritis, ANA and some other subphenotypes of the disease.
Our findings suggest that SNP rs2230926 in the TNFAIP3 might be a common genetic factor for SLE within different populations
in terms of Chinese Han and European population. 相似文献
35.
Wei Li Yi-Min Tao Yun Tang Xue-Jun Xu Jie Chen Wei Fu Xing-Hai Wang Bo Chao Wei Sheng Qiong Xie Zhui-Bai Qiu Jing-Gen Liu 《Bioorganic & medicinal chemistry letters》2010,20(1):418-421
Unexpected substituent on the well-known morphine skeleton is described to be account for highly selective and potent μ opioid ligands, which is strongly connected to substituted aromatic groups on this omitted 8α-position. 相似文献
36.
? Premise of the study: Microsatellite markers were developed for Ptychomitrium gardneri to study population genetics of this eastern Asian-North American disjunct moss. ? Methods and Results: A total of 13 microsatellite markers were developed in Chinese populations of P. gardneri, using the Fast Isolation by AFLP of Sequences COntaining Repeats protocol. Eight of the markers showed polymorphism when assessed in a sample of four populations of 29 individuals from China. These markers amplified three to four alleles per locus. Five primers also amplified in P. linearifolium and P. wilsonii. ? Conclusions: These markers may be useful for further investigation of population genetics of P. gardneri. 相似文献
37.
? Premise of the study: Microsatellite markers were developed to help elucidate the population genetics of the invasive species Wedelia trilobata. ? Methods and Results: Using the Fast Isolation by AFLP of Sequences COntaining (FIASCO) repeats protocol, 23 sets of primers for amplifying microsatellite loci were identified in W. trilobata, 10 of which showed polymorphism (two to five alleles per locus) in samples of two populations of W. trilobata, one from China and one from Peru. Six of these loci were successfully amplified from samples of the native congener W. chinensis, with expected sizes. ? Conclusions: These markers may be useful for further investigation of population genetics of Wedelia trilobata and other congener species. 相似文献
38.
39.
Long Jun-Yi Wang Xue-Jun Li Xiao-Ying Kong Xie-He Yang Guang Zhang Dan Yang Yan-Ting Shi Zheng Ma Xiao-Peng 《Neurochemical research》2022,47(3):545-551
Neurochemical Research - Chronic visceral pain (CVP) is one of the common symptoms of many diseases triggered by underlying diseases of the internal organs of the human body. Its causes include... 相似文献
40.