全文获取类型
收费全文 | 666篇 |
免费 | 36篇 |
国内免费 | 36篇 |
专业分类
耳鼻咽喉 | 3篇 |
儿科学 | 54篇 |
妇产科学 | 8篇 |
基础医学 | 62篇 |
口腔科学 | 16篇 |
临床医学 | 90篇 |
内科学 | 160篇 |
皮肤病学 | 5篇 |
神经病学 | 17篇 |
特种医学 | 162篇 |
外科学 | 39篇 |
综合类 | 12篇 |
预防医学 | 24篇 |
眼科学 | 8篇 |
药学 | 44篇 |
肿瘤学 | 34篇 |
出版年
2024年 | 2篇 |
2023年 | 2篇 |
2021年 | 5篇 |
2020年 | 3篇 |
2019年 | 6篇 |
2018年 | 11篇 |
2017年 | 7篇 |
2016年 | 4篇 |
2015年 | 7篇 |
2014年 | 15篇 |
2013年 | 20篇 |
2012年 | 11篇 |
2011年 | 13篇 |
2010年 | 38篇 |
2009年 | 38篇 |
2008年 | 19篇 |
2007年 | 31篇 |
2006年 | 11篇 |
2005年 | 17篇 |
2004年 | 7篇 |
2003年 | 6篇 |
2002年 | 10篇 |
2001年 | 12篇 |
2000年 | 5篇 |
1999年 | 7篇 |
1998年 | 48篇 |
1997年 | 48篇 |
1996年 | 45篇 |
1995年 | 40篇 |
1994年 | 41篇 |
1993年 | 26篇 |
1992年 | 3篇 |
1991年 | 12篇 |
1990年 | 11篇 |
1989年 | 25篇 |
1988年 | 23篇 |
1987年 | 12篇 |
1986年 | 15篇 |
1985年 | 9篇 |
1984年 | 7篇 |
1983年 | 6篇 |
1982年 | 10篇 |
1981年 | 8篇 |
1980年 | 10篇 |
1979年 | 5篇 |
1978年 | 6篇 |
1977年 | 10篇 |
1976年 | 6篇 |
1975年 | 3篇 |
1969年 | 1篇 |
排序方式: 共有738条查询结果,搜索用时 265 毫秒
731.
Using a mouse model we show that self-complementary (sc) adeno-associated virus (AAV) vectors pseudotyped with capsids of serotypes 2, 7 or 8 induce more potent transgene product-specific CD8(+) T cell and antibody responses compared to corresponding single-stranded (ss)AAV vectors. These data suggest that the higher and more rapidly appearing amounts of transgene product achieved with scAAV vectors may increase detrimental immune responses in gene transfer recipients. 相似文献
732.
CJ Ledgerwood SM Greenwood RR Brett JA Pratt TJ Bushell 《British journal of pharmacology》2011,162(1):286-294
BACKGROUND AND PURPOSE
Cannabidiol (CBD) has emerged as an interesting compound with therapeutic potential in several CNS disorders. However, whether it can modulate synaptic activity in the CNS remains unclear. Here, we have investigated whether CBD modulates synaptic transmission in rat hippocampal cultures and acute slices.EXPERIMENTAL APPROACH
The effect of CBD on synaptic transmission was examined in rat hippocampal cultures and acute slices using whole cell patch clamp and standard extracellular recordings respectively.KEY RESULTS
Cannabidiol decreased synaptic activity in hippocampal cultures in a concentration-dependent and Pertussis toxin-sensitive manner. The effects of CBD in culture were significantly reduced in the presence of the cannabinoid receptor (CB1) inverse agonist, but were unaffected by the 5-HT1A receptor antagonist, WAY100135. In hippocampal slices, CBD inhibited basal synaptic transmission, an effect that was abolished by the proposed CB1 receptor antagonist, AM251, in addition to LY320135 and WAY100135. LY320135CONCLUSIONS AND IMPLICATIONS
Cannabidiol reduces synaptic transmission in hippocampal in vitro preparations and we propose a role for both 5-HT1A and CB1 receptors in these CBD-mediated effects. These data offer some mechanistic insights into the effects of CBD and emphasize that further investigations into the actions of CBD in the CNS are required in order to elucidate the full therapeutic potential of CBD. 相似文献733.
MS Hildebrand NP Thorne CJ Bromhead K Kahrizi JA Webster Z Fattahi M Bataejad WJ Kimberling D Stephan H Najmabadi M Bahlo RJH Smith 《Clinical genetics》2010,77(6):563-571
Hildebrand MS, Thorne NP, Bromhead CJ, Kahrizi K, Webster JA, Fattahi Z, Bataejad M, Kimberling WJ, Stephan D, Najmabadi H, Bahlo M, Smith RJH. Variable hearing impairment in a DFNB2 family with a novel MYO7A missense mutation. Myosin VIIA mutations have been associated with non‐syndromic hearing loss (DFNB2; DFNA11) and Usher syndrome type 1B (USH1B). We report clinical and genetic analyses of a consanguineous Iranian family segregating autosomal recessive non‐syndromic hearing loss (ARNSHL). The hearing impairment was mapped to the DFNB2 locus using Affymetrix 50K GeneChips; direct sequencing of the MYO7A gene was completed. The Iranian family (L‐1419) was shown to segregate a novel homozygous missense mutation (c.1184G>A) that results in a p.R395H amino acid substitution in the motor domain of the myosin VIIA protein. As one affected family member had significantly less severe hearing loss, we used a candidate approach to search for a genetic modifier. This novel MYO7A mutation is the first reported to cause DFNB2 in the Iranian population and this DFNB2 family is the first to be associated with a potential modifier. The absence of vestibular and retinal defects, and less severe low frequency hearing loss, is consistent with the phenotype of a recently reported Pakistani DFNB2 family. Thus, we conclude this family has non‐syndromic hearing loss (DFNB2) rather than USH1B, providing further evidence that these two diseases represent discrete disorders. 相似文献
734.
CRM Lammens EMA Bleiker S Verhoef FJ Hes MGEM Ausems D Majoor‐Krakauer RH Sijmons RB Van Der Luijt AMW Van Den Ouweland Tam Van Os N Hoogerbrugge EB Gómez García CJ Dommering CM Gundy NK Aaronson 《Clinical genetics》2010,77(5):483-491
Lammens CRM, Bleiker EMA, Verhoef S, Hes FJ, Ausems MGEM, Majoor‐Krakauer D, Sijmons RH, Luijt van der RB, Ouweland van den AMW, Van Os Tam, Hoogerbrugge N, Gomez‐Garcia EB, Dommering CJ, Gundy CM, Aaronson NK. Psychosocial impact of von Hippel–Lindau disease: levels and sources of distress. Von Hippel–Lindau disease (VHL) is a hereditary tumor susceptibility syndrome, characterized by an increased risk of developing multiple benign and malignant tumors at various sites and ages with limited preventive options. This study evaluates the prevalence of distress among VHL family members and factors associated significantly with such distress. Forty‐eight families with a VHL mutation were identified via the nine family cancer clinics in the Netherlands. In total, 171 family members (carriers, 50% at‐risk, non‐carriers) were approached, of whom 123 (72%) completed a self‐report questionnaire. Approximately 40% of the VHL family members reported clinically relevant levels of distress, approaching 50% among the carriers and, possibly even more striking, 36% among the non‐carriers. Having lost a first degree relative due to VHL during adolescence (OR 11.2; 95% CI 1.4–86.9) was related significantly to heightened levels of distress. Approximately, only one‐third of those who reported heightened levels of distress had received professional psychosocial support. A substantial percentage of family members experience clinically relevant levels of distress. We would recommend the introduction of a procedure for screening for distress in this vulnerable population. Special attention should be paid to those individuals who have lost a close relative due to VHL during adolescence. 相似文献
735.
Although the dominant approach to drug development is the design of compounds selective for a given target, compounds targeting more than one biological process may have superior efficacy, or alternatively a better safety profile than standard selective compounds. Here, this possibility has been explored with respect to the endocannabinoid system and pain. Compounds inhibiting the enzyme fatty acid amide hydrolase (FAAH), by increasing local endocannabinoid tone, produce potentially useful effects in models of inflammatory and possibly neuropathic pain. Local increases in levels of the endocannabinoid anandamide potentiate the actions of cyclooxygenase inhibitors, raising the possibility that compounds inhibiting both FAAH and cyclooxygenase can be as effective as non-steroidal anti-inflammatory drugs but with a reduced cyclooxygenase inhibitory ‘load’. An ibuprofen analogue active in models of visceral pain and with FAAH and cyclooxygenase inhibitory properties has been identified. Another approach, built in to the experimental analgesic compound N-arachidonoylserotonin, is the combination of FAAH inhibitory and transient receptor potential vanilloid type 1 antagonist properties. Although finding the right balance of actions upon the two targets is a key to success, it is hoped that dual-action compounds of the types illustrated in this review will prove to be useful analgesic drugs. 相似文献
736.
Solberg BC Dirksen CD Nieman FH van Merode G Poeze M Ramsay G 《Critical care (London, England)》2008,12(3):R68
Introduction
The high cost of critical care resources has resulted in strategies to reduce the costs of ruling out low-risk patients by developing intermediate care units (IMCs). The aim of this study was to compare changes in total hospital costs for intensive care patients before and after the introduction of an IMC at the University Hospital Maastricht. 相似文献737.
CJ. Zhao C. Noack M. Brackmann T. Gloveli A. Maelicke U. Heinemann R. Anand K.H. Braunewell 《Molecular and cellular neurosciences》2009,40(2):280-292
The neuronal Ca2+-sensor protein VILIP-1, known to affect clathrin-dependent receptor trafficking, has been shown to interact with the cytoplasmic loop of the α4-subunit of the α4β2 nicotinic acetylcholine receptor (nAChR), which is the most abundant nAChR subtype with high-affinity for nicotine in the brain. The α4β2 nAChR is crucial for nicotine addiction and the beneficial effects of nicotine on cognition. Its dysfunction has been implicated in frontal lobe epilepsy, Alzheimer's disease and schizophrenia. Here we report that overexpression of VILIP-1 enhances ACh responsiveness, whereas siRNA against VILIP-1 reduces α4β2 nAChR currents of hippocampal neurons. The underlying molecular mechanism likely involves enhanced constitutive exocytosis of α4β2 nAChRs mediated by VILIP-1. The two interaction partners co-localize in a Ca2+-dependent manner with syntaxin-6, a Golgi-SNARE protein involved in trans-Golgi membrane trafficking. Thus, we speculate that regulation of VILIP-1-expression might modulate surface expression of ligand-gated ion channels, such as the α4β2 nAChRs, possibly comprising a novel form of physiological up-regulation of ligand-gated ion channels. 相似文献