全文获取类型
收费全文 | 3986篇 |
免费 | 400篇 |
国内免费 | 1653篇 |
出版年
2024年 | 33篇 |
2023年 | 106篇 |
2022年 | 164篇 |
2021年 | 195篇 |
2020年 | 194篇 |
2019年 | 168篇 |
2018年 | 146篇 |
2017年 | 129篇 |
2016年 | 183篇 |
2015年 | 219篇 |
2014年 | 291篇 |
2013年 | 337篇 |
2012年 | 418篇 |
2011年 | 389篇 |
2010年 | 297篇 |
2009年 | 285篇 |
2008年 | 380篇 |
2007年 | 354篇 |
2006年 | 313篇 |
2005年 | 303篇 |
2004年 | 195篇 |
2003年 | 189篇 |
2002年 | 168篇 |
2001年 | 107篇 |
2000年 | 122篇 |
1999年 | 69篇 |
1998年 | 45篇 |
1997年 | 40篇 |
1996年 | 38篇 |
1995年 | 37篇 |
1994年 | 24篇 |
1993年 | 27篇 |
1992年 | 12篇 |
1991年 | 11篇 |
1990年 | 4篇 |
1989年 | 3篇 |
1988年 | 8篇 |
1987年 | 7篇 |
1986年 | 1篇 |
1985年 | 9篇 |
1984年 | 2篇 |
1983年 | 4篇 |
1982年 | 4篇 |
1981年 | 5篇 |
1980年 | 1篇 |
1979年 | 2篇 |
1978年 | 1篇 |
排序方式: 共有6039条查询结果,搜索用时 31 毫秒
1.
Jianhua Zhang Mei Liu Hongjian Jin Liandong Deng Jinfeng Xing Anjie Dong 《AAPS PharmSciTech》2010,11(2):894-903
Lactate esters are widely used as food additives, perfume materials, medicine additives, and personal care products. The objective
of this work was to investigate the effect of a series of lactate esters as penetration enhancers on the in vitro skin permeation of four drugs with different physicochemical properties, including ibuprofen, salicylic acid, dexamethasone
and 5-fluorouracil. The saturated donor solutions of the evaluated drugs in propylene glycol were used in order to keep a
constant driving force with maximum thermodynamic activity. The permeability coefficient (K
p), skin concentration of drugs (SC), and lag time (T), as well as the enhancement ratios for K
p and SC were recorded. All results indicated that lactate esters can exert a significant influence on the transdermal delivery
of the model drugs and there is a structure-activity relationship between the tested lactate esters and their enhancement
effects. The results also suggested that the lactate esters with the chain length of fatty alcohol moieties of 10–12 are more
effective enhancers. Furthermore, the enhancement effect of lactate esters increases with a decrease of the drug lipophilicity,
which suggests that they may be more efficient at enhancing the penetration of hydrophilic drugs than lipophilic drugs. The
influence of the concentration of lactate esters was evaluated and the optimal concentration is in the range of 5∼10 wt.%.
In sum, lactate esters as a penetration enhancer for some drugs are of interest for transdermal administration when the safety
of penetration enhancers is a prime consideration. 相似文献
2.
为了解内蒙古地区蜱虫病毒组学的本底数据,采用病毒宏基因组学方法对在内蒙古阿拉善盟左旗、右旗和四子王旗地区3个采样点采集骆驼和羊体表寄生的1789只蜱虫样品进行病毒宏基因组学分析,并对特定病毒进行巢式PCR扩增和测序,通过Clustal W和MEGA7.0等生物信息学软件对获得的病毒基因序列进行遗传进化分析.数据显示,蜱虫样品携带包括植物、脊椎动物和非脊椎动物等来源的17个病毒科和一些未分类的病毒;其中,2株弹状病毒具有丰富的遗传多样性,与新疆地区和长江地区的弹状病毒的同源性达到98.5%和96.26%,提示蜱虫弹状病毒可能是通过羊和骆驼等动物贸易导致了新疆和内蒙古地区,以及内地的跨区域传播;细小病毒仅在羊来源的蜱虫中检测到,与中国河北地区的山羊血清中的细小病毒形成同一进化分支,我们推测蜱虫细小病毒在国内不同地区间可跨区域传播,在进化分析过程中,发现这种病毒与多种的细小病毒的同源性都不低于50%,提示细小病毒可能具有遗传稳定性;Tamdy病毒与来自阿塞拜疆、乌兹别克斯坦和美国的Tamdy病毒均具有极高的同源性,结果显示该病毒在内蒙古地区已经出现,并存在潜在流行的可能,有必要对Tamdy病毒进行进一步的监测;在本研究中,我们鉴定的白蛉病毒与来自新疆的亚洲璃眼蜱所携带的博乐蜱虱病毒形成同一个进化分支,与新型布尼亚病毒和Heartland virus病毒的同源性达到50%以上,该结果提示,我们发现的蜱虫白蛉病毒可能具有潜在的致病性,需要对其流行情况和致病性进行监测和研究.本研究为完善内蒙古部分地区蜱虫病毒的多样性和本底情况提供了重要的基础数据. 相似文献
3.
Peng Wang Ronghua Luo Min Zhang Yaqing Wang Tianzhang Song Tingting Tao Zhongyu Li Lin Jin Hongyi Zheng Wenwen Chen Mengqian Zhao Yongtang Zheng Jianhua Qin 《Cell death & disease》2020,11(12)
COVID-19, caused by SARS-CoV-2, is an acute and rapidly developing pandemic, which leads to a global health crisis. SARS-CoV-2 primarily attacks human alveoli and causes severe lung infection and damage. To better understand the molecular basis of this disease, we sought to characterize the responses of alveolar epithelium and its adjacent microvascular endothelium to viral infection under a co-culture system. SARS-CoV-2 infection caused massive virus replication and dramatic organelles remodeling in alveolar epithelial cells, alone. While, viral infection affected endothelial cells in an indirect manner, which was mediated by infected alveolar epithelium. Proteomics analysis and TEM examinations showed viral infection caused global proteomic modulations and marked ultrastructural changes in both epithelial cells and endothelial cells under the co-culture system. In particular, viral infection elicited global protein changes and structural reorganizations across many sub-cellular compartments in epithelial cells. Among the affected organelles, mitochondrion seems to be a primary target organelle. Besides, according to EM and proteomic results, we identified Daurisoline, a potent autophagy inhibitor, could inhibit virus replication effectively in host cells. Collectively, our study revealed an unrecognized cross-talk between epithelium and endothelium, which contributed to alveolar–capillary injury during SARS-CoV-2 infection. These new findings will expand our understanding of COVID-19 and may also be helpful for targeted drug development.Subject terms: Mechanisms of disease, Viral infection 相似文献
4.
Dongliang Liu Jun Liu Weilan Wang Lijie Xia Jianhua Yang Surong Sun Fuchun Zhang 《Food biophysics》2016,11(4):319-331
Cecropin XJ, as a heat stable antimicrobial peptide (AMP), displayed broad bacteriostatic activities, effectively inhibited proliferation of cancer cells and induced cell apoptosis in vitro. However, it exhibited little hemolytic activity and very low cytotoxicity to erythrocytes and normal cells. Although exerts multiple remarkable bioactivities, the refined molecular conformation of native Cecropin XJ remains unsolved. The aim of the present study is to comprehensively investigate the physicochemical characteristics and structure-function relationship of this antimicrobial peptide by using a series of bioinformatics and experimental approaches. In this study, we revealed that the mature Cecropin XJ consists of 41 amino acids, containing two α-helical structures from Lys7 to Lys25 and from Ala29 to Ile39. The phylogenetic tree indicated that Cecropin XJ belongs to the Class I AMPs of cecropin family. Hydrophobic analysis showed Cecropin XJ is a typical amphiphilic molecule. The surface of Cecropin XJ was found to have a much wide range of electrostatic potential from ?83.243 to +83.243. The amphipathicity and surface potential of Cecropin XJ partially supported the AMP pore-forming hypothesis. Scanning electron microscopy experimentally confirmed the damages of Cecropin XJ to microbial membrane. Four predicted docking sites respectively for magnesium ion (Mg2+), adenosine diphosphate (ADP), bacteriopheophytin (BPH), and guanosine triphosphate (GTP) were found on the surface of Cecropin XJ. Thereinto, Mg2+ was experimentally proved to suppress the antibacterial activity of Cecropin XJ; both GTP and ADP enhanced the bactericidal activities to varying degrees. The present study provides a foundation for further investigation of molecular evolution, structural modification, and functional mechanisms of Cecropin XJ. 相似文献
5.
6.
Ke Wang Feiyun Xu Wei Yuan Dongping Zhang Jianping Liu Leyun Sun Liyou Cui Jianhua Zhang Weifeng Xu 《The Plant journal : for cell and molecular biology》2021,107(6):1603-1615
Heterotrimeric G protein is involved in plant growth and development, while the role of rice (Oryza sativa) G protein γ subunit qPE9-1 in response to low-phosphorus (LP) conditions remains unclear. The gene expression of qPE9-1 was significantly induced in rice roots under LP conditions. Rice varieties carrying the qPE9-1 allele showed a stronger primary root response to LP than the varieties carrying the qpe9-1 allele (mutant of the qPE9-1 allele). Transgenic rice plants with the qPE9-1 allele had longer primary roots and higher P concentrations than those with the qpe9-1 allele under LP conditions. The plasma membrane (PM) H+-ATPase was important for the qPE9-1-mediated response to LP. Furthermore, OsGF14b, a 14-3-3 protein that acts as a key component in activating PM H+-ATPase for root elongation, is also involved in the qPE9-1 mediation. Moreover, the overexpression of OsGF14b in WYJ8 (carrying the qpe9-1 allele) partially increased primary root length under LP conditions. Experiments using R18 peptide (a 14-3-3 protein inhibitor) showed that qPE9-1 is important for primary root elongation and H+ efflux under LP conditions by involving the 14-3-3 protein. In addition, rhizosheath weight, total P content, and the rhizosheath soil Olsen-P concentration of qPE9-1 lines were higher than those of qpe9-1 lines under soil drying and LP conditions. These results suggest that the G protein γ subunit qPE9-1 in rice plants modulates root elongation for phosphorus uptake by involving the 14-3-3 protein OsGF14b and PM H+-ATPase, which is required for rice P use. 相似文献
7.
在鉴定我囱青海省单蚤属(Monopsyllus Kolenati,1857)的跳蚤标本时,除检出别人已记述过的不等单蚤[Monopsyllus anisus(Rotnschild,1907)],新月单蚤(Monopsyllusscaloni Vovchinskaya,1950)和冯氏单蚤(Monopsyllus fengi Liu,Xie et Wang)(新种,待发表)外,尚发现两个在形态上都接近花鼠单蚤[Monopsyllus indages(Rothschild,1908)]的新种。由于两新种阳茎钩突特别,故分别命名为钩状单蚤Monopsyllus hamutus,新种和文状单蚤Monopsyllus forficus,新种。鉴别这三个蚤种的重要特征如表1所示。 相似文献
8.
胆碱能神经对人餐后神经降压素释放的影响 总被引:2,自引:0,他引:2
本文比较了6名健康成人进食、餐前肌注阿托品以及单纯咀嚼食物后的血浆神经降压素样免疫活性物质(NTLI)水平的变化,以探讨胆碱能神经对神经降压素释放的影响。用放射免疫测定法分别测定NTLI和胰多肽(PP)的含量,以便同时比较两者释放的状态。6人的基础血浆NTLI和PP的水平平均分别为15.7±2.4和16.6±9 7pmol/L。进食后,血浆NTLI和PP水平均显著增高,并呈双相反应。第一个血浆NTLI高峰平均为60.7±13.2pmol/L,出现于餐后的20min。餐后90min,又出现另一个高峰,其平均水平为58.8±8.2pmol/L。在进食前肌注阿托品1mg,餐后的第一个血浆NTLI高峰消失,而第二个高峰仍存在。单纯咀嚼食物后,血浆PP水平明显增高,而对NTLI的释放无刺激作用。本文结果提示,餐后早期的神经降压素释放的调节是由非迷走胆碱能神经参与的,而后期的释放不受胆碱能神经的影响。 相似文献
9.
Sand burial effects on seed germination, seedling emergence and establishment of Panicum virgatum 总被引:5,自引:0,他引:5
Studies in the field and in a greenhouse were conducted to examine the effects of sand burial on seed germination, seedling emergence and establishment of Panicum virgatum L. on the foredunes of Lake Erie. Under natural conditions, the seedlings emerged from sand burial depths ranging from 0 to 11 cm, with a mean ± SD of 4.73 ± 1.82 cm. The frequency distribution of the depth of emergence of seedlings in the field was significantly skewed to the right and platykurtic. In the greenhouse, some seedlings emerged from a burial depth of as much as 16 cm. Although percent germination of seeds was not affected by sand burial, the percent emergence and the rate of emergence of seedlings were significantly reduced by excessive sand burial. Seedling mortality was found only among seedlings that emerged from sand burial depths of 10 cm or more. In the field, all the seedlings established in one growing season had originally emerged from sand burial depths of less than 12 cm. Within this burial range, seedlings from shallower burial depths had lower chances of establishment than expected, whereas those from deeper burial depths had higher probabilities of establishment than expected. 相似文献
10.