全文获取类型
收费全文 | 1616篇 |
免费 | 128篇 |
国内免费 | 61篇 |
专业分类
耳鼻咽喉 | 5篇 |
儿科学 | 69篇 |
妇产科学 | 10篇 |
基础医学 | 95篇 |
口腔科学 | 7篇 |
临床医学 | 48篇 |
内科学 | 77篇 |
皮肤病学 | 2篇 |
神经病学 | 480篇 |
特种医学 | 9篇 |
外国民族医学 | 2篇 |
外科学 | 61篇 |
综合类 | 90篇 |
预防医学 | 139篇 |
眼科学 | 10篇 |
药学 | 527篇 |
中国医学 | 39篇 |
肿瘤学 | 135篇 |
出版年
2024年 | 1篇 |
2023年 | 23篇 |
2022年 | 25篇 |
2021年 | 44篇 |
2020年 | 49篇 |
2019年 | 57篇 |
2018年 | 47篇 |
2017年 | 70篇 |
2016年 | 51篇 |
2015年 | 56篇 |
2014年 | 79篇 |
2013年 | 145篇 |
2012年 | 79篇 |
2011年 | 87篇 |
2010年 | 71篇 |
2009年 | 54篇 |
2008年 | 58篇 |
2007年 | 81篇 |
2006年 | 65篇 |
2005年 | 62篇 |
2004年 | 46篇 |
2003年 | 53篇 |
2002年 | 55篇 |
2001年 | 41篇 |
2000年 | 35篇 |
1999年 | 30篇 |
1998年 | 24篇 |
1997年 | 31篇 |
1996年 | 23篇 |
1995年 | 36篇 |
1994年 | 16篇 |
1993年 | 14篇 |
1992年 | 22篇 |
1991年 | 19篇 |
1990年 | 15篇 |
1989年 | 15篇 |
1988年 | 10篇 |
1987年 | 6篇 |
1986年 | 16篇 |
1985年 | 28篇 |
1984年 | 27篇 |
1983年 | 17篇 |
1982年 | 5篇 |
1981年 | 4篇 |
1980年 | 8篇 |
1978年 | 4篇 |
1976年 | 1篇 |
排序方式: 共有1805条查询结果,搜索用时 62 毫秒
1.
Jennifer M. Sasaki Russell Gregory A. Chinn Deenu Maharjan Yasmine Eichbaum Jeffrey W. Sall 《British journal of anaesthesia》2019,122(4):490-499
Background
The factors determining peak susceptibility of the developing brain to anaesthetics are unclear. It is unknown why postnatal day 7 (P7) male rats are more vulnerable to anaesthesia-induced memory deficits than littermate females. Given the precocious development of certain regions in the female brain during the neonatal critical period, we hypothesised that females are susceptible to anaesthetic brain injury at an earlier time point than previously tested.Methods
Female rats were exposed to isoflurane (Iso) 1 minimum alveolar concentration or sham anaesthesia at P4 or P7. Starting at P35, rats underwent a series of behavioural tasks to test their spatial and recognition memory. Cell death immediately after anaesthesia was quantified by Fluoro-Jade C staining in select brain regions, and developmental expression of the chloride transporters KCC2 and NKCC1 was analysed by immunoblotting in male and female rats at P4 and P7.Results
Female rats exposed to Iso at P4 displayed impaired spatial, object-place, -context, and social recognition memory, and increased cell death in the hippocampus and laterodorsal thalamus. Female rats exposed at P7 exhibited only decreased performance in object-context compared with control. The ratio of NKCC1/KCC2 expression in cerebral cortex was higher in P4 females than in P7 females, and similar to that in P7 males.Conclusions
Female rats exposed to Iso at P4 are sensitive to anaesthetic injury historically observed in P7 males. This is consistent with a comparably immature developmental state in P4 females and P7 males. The window of anaesthetic vulnerability correlates with sex-specific cortical expression of chloride transporters NKCC1 and KCC2. These findings suggest that both sex and developmental age play important roles in determining the outcome after early anaesthesia exposure. 相似文献2.
3.
Valentina Bashkatova 《World Journal of Psychiatry》2021,11(10):830-840
Dopaminergic neurotoxicity is characterized by damage and death of dopaminergic neurons. Parkinson's disease (PD) is a neurodegenerative disorder that primarily involves the loss of dopaminergic neurons in the substantia nigra. Therefore, the study of the mechanisms, as well as the search for new targets for the prevention and treatment of neurodegenerative diseases, is an important focus of modern neuroscience. PD is primarily caused by dysfunction of dopaminergic neurons; however, other neurotransmitter systems are also involved. Research reports have indicated that the glutamatergic system is involved in different pathological conditions, including dopaminergic neurotoxicity. Over the last two decades, the important functional interplay between dopaminergic and glutamatergic systems has stimulated interest in the possible role of metabotropic glutamate receptors (mGluRs) in the development of extrapyramidal disorders. However, the specific mechanisms driving these processes are presently unclear. The participation of the universal neuronal messenger nitric oxide (NO) in the mechanisms of dopaminergic neurotoxicity has attracted increased attention. The current paper aims to review the involvement of mGluRs and the contribution of NO to dopaminergic neurotoxicity. More precisely, we focused on studies conducted on the rotenone-induced PD model. This review is also an outline of our own results obtained using the method of electron paramagnetic resonance, which allows quantitation of NO radicals in brain structures. 相似文献
4.
5.
Ismail O. Ishola Onyinyechi E. Akataobi Azeez A. Alade Olufunmilayo O. Adeyemi 《Fundamental & clinical pharmacology》2019,33(3):277-285
There is a growing number of epidemiological and molecular studies which suggest that diabetes is associated with an increased risk of Parkinson's disease (PD). Hence, in this study, the effect of glimepiride (GPD), a sulphonylurea (antidiabetic) on paraquat (PQT)‐induced Parkinsonism was evaluated in mice. Thirty‐six mice were randomly divided into six groups (n = 6) and treated orally for 21 consecutive days as follows: Group 1: vehicle (10 mL/kg), Group 2: PQT (10 mg/kg, i.p., twice per week for 3 weeks), Group 3–5: GPD (1, 2 or 4 mg/kg) + PQT (10 mg/kg, i.p., twice per week for 3 weeks), Group 6: GPD (4 mg/kg, p.o.). The effects of the treatment on motor coordination were evaluated using the rotarod performance, bar and open field tests while working memory was assayed using Y‐maze test. Paraquat injection induced significant decrease in falling time, number of crosses and percentage alternation behaviour with a concomitant increase in the duration of cataleptic behaviour in the rotarod, open field, Y‐maze and bar tests, respectively, which was ameliorated by GPD treatment. PQT also increased lipid peroxidation, peroxynitrite and TNF‐α generations as well as deficit in superoxide dismutase and GSH activities in the midbrain. PQT‐induced oxidative stress and neuroinflammation was attenuated by GPD treatment. Findings from this study showed that GPD prevents PQT‐induced motor dysfunction, memory impairment, oxidative stress and neuroinflammation through enhancement of antioxidant defense system and inhibition of pro‐inflammatory cytokine release. Thus, GPD could be a potential adjunct in the management of Parkinsonism. 相似文献
6.
7.
Govindaraj Saravanan Theivendren Panneerselvam Selvaraj Kunjiappan Pavadai Parasuraman Veerachamy Alagarsamy Padmaja Udayakumar Muthukrishnan Soundararajan Shrinivas D. Joshi Suresh Ramalingam Damodar Nayak Ammunje 《Drug development research》2019,80(3):368-385
Hit, Lead & Candidate Discovery |
8.
Wei Zhang Zheng Li Feng-Qing Xu Ya-Shuo Ren Shuang-Wang Xu Tong-Sheng Wang 《Journal of Asian natural products research》2019,21(5):426-434
Two new 11-methoxyl substituted triterpenoids, named as mimengosides J (1) and K (2), along with seven known compounds, were isolated from the fruits of Buddleja lindleyana. Their structures were elucidated on the basis of spectroscopic analysis. In addition, the new ones were evaluated for protective effects against damage of SH-SY5Y cells induced by 1-methyl-4-phenylpyridinium ion (MPP+) and the results indicated that those may be one of the candidate compositions of Buddleja lindleyana for the treatment of neurodegenerative disease.
9.
Dana Franzen-Klein Mark Jankowski Charlotte L. Roy Hoa Nguyen-Phuc Da Chen Lorin Neuman-Lee 《Journal of toxicology and environmental health. Part A》2020,83(2):45-65
ABSTRACTDomestic chickens (Gallus gallus domesticus) were exposed to imidacloprid by gavage once daily for 7 consecutive days at 0, 0.03, 0.34, 3.42, 10.25, and 15.5 mg/kg/day (n = 20 per group; 5 6-week-old males, 5 6-week-old females, 5 9-week-old males, and 5 9-week-old females). The severity and duration of neurobehavioral abnormalities were recorded. Components of the innate and adaptive immune system were assessed with 7 standard functional assays. Temporary neurobehavioral abnormalities were observed in a dose-dependent manner, including muscle tremors, ataxia, and depressed mentation. Based upon mean clinical severity scores, the no observed adverse effect level (NOAEL) was 3.42 mg/kg/day, and the lowest observed adverse effect level (LOAEL) was 10.25 mg/kg/day. The effective dose value for the presence of any neurobehavioral abnormalities in 50% of the test group (ED50) was 4.62 ± 0.98 mg/kg/day. The ED50 for an adjusted score that included both severity and duration of neurobehavioral abnormalities was 11.24 ± 9.33 mg/kg/day. These ED50 values are equivalent to a 1 kg bird ingesting 29 or 70 imidacloprid treated soybean seeds respectively. Immunotoxicity was not documented, possible causes include the assays were insensitive, relevant immune functions were not examined, or imidacloprid is not immunotoxic at this dosing schedule in this species. Neurobehavioral abnormalities were a more sensitive indicator of the sublethal effects of imidacloprid than immunotoxicity. 相似文献
10.
目的 探讨观察母孕鼠围产期全氟辛烷磺酸盐(perfluorooctane sulphonate,PFOS)暴露对幼鼠海马组织BDNF/TrkB/CREB信号通路关键基因表达的影响。 方法 20只昆明种雌性小鼠随机分为对照组和低、中、高剂量组,从孕鼠怀孕第2 d开始(gestation day2, GD2)到幼鼠出生后21 d(postnatal day21,PND21)分别给予低、中、高剂量组孕鼠PFOS剂量为 0.1、1.0、5.0 mg/(kg·bw)灌胃染毒,对照组给予等体积的0.05% Tween-20水溶液。灌胃量为0.1 ml/10 (g·bw)。PND 21 d处死幼鼠,收集脑组织,分离海马及皮层。HE染色观察脑组织常规病理改变,实时荧光定量PCR(Quantitative Real-time PCR,QPCR)检测海马组织中BDNF、TrkB、CREB、Syn1及Syp的mRNA表达水平。 结果 与对照组相比较,低、中、高三个剂量组对幼鼠的死亡率和体质量的影响差异无统计学意义(P>0.05)。但是在高剂量组幼鼠海马组织出现空泡,海马BDNF、TrkB、CREB mRNA水平显著降低,分别由对照组的(0.98±0.11)、(1.03±0.09)、(1.08±0.12)下降到(0.22±0.21)、(0.71±0.14)、(0.37±0.26),并在中、高剂量组引起了幼鼠突触相关蛋白Syn1和Spy的mRNA水平显著降低,分别由对照组的(1.10±0.09)、(0.97±0.08)下降到中剂量的(0.41±0.23)、(0.71±0.17)和高剂量的(0.39±0.19)、(0.63±0.19),差异均有统计学意义(P<0.05)。 结论 PFOS损伤海马BDNF/TrkB/CREB信号通路可能是PFOS神经发育毒性之一。 相似文献