全文获取类型
收费全文 | 2024篇 |
免费 | 164篇 |
国内免费 | 82篇 |
出版年
2024年 | 14篇 |
2023年 | 57篇 |
2022年 | 50篇 |
2021年 | 80篇 |
2020年 | 113篇 |
2019年 | 133篇 |
2018年 | 118篇 |
2017年 | 91篇 |
2016年 | 76篇 |
2015年 | 70篇 |
2014年 | 127篇 |
2013年 | 208篇 |
2012年 | 96篇 |
2011年 | 111篇 |
2010年 | 83篇 |
2009年 | 111篇 |
2008年 | 126篇 |
2007年 | 107篇 |
2006年 | 97篇 |
2005年 | 92篇 |
2004年 | 59篇 |
2003年 | 37篇 |
2002年 | 62篇 |
2001年 | 30篇 |
2000年 | 14篇 |
1999年 | 15篇 |
1998年 | 12篇 |
1997年 | 14篇 |
1996年 | 7篇 |
1995年 | 6篇 |
1994年 | 6篇 |
1993年 | 4篇 |
1992年 | 3篇 |
1991年 | 9篇 |
1990年 | 4篇 |
1989年 | 4篇 |
1988年 | 2篇 |
1987年 | 1篇 |
1986年 | 5篇 |
1984年 | 5篇 |
1983年 | 1篇 |
1982年 | 1篇 |
1981年 | 3篇 |
1980年 | 1篇 |
1979年 | 1篇 |
1977年 | 1篇 |
1975年 | 1篇 |
1973年 | 1篇 |
1950年 | 1篇 |
排序方式: 共有2270条查询结果,搜索用时 15 毫秒
991.
Markus A. Moosmeier Julia Bulkescher Jennifer Reed Martina Schnölzer Hans Heid Karin Hoppe‐Seyler Felix Hoppe‐Seyler 《Journal of cellular and molecular medicine》2010,14(7):1935-1945
The delivery of molecules into cells poses a critical problem that has to be solved for the development of diagnostic tools and therapeutic agents acting on intracellular targets. Cargos which by themselves cannot penetrate cellular membranes due to their biophysical properties can achieve cell membrane permeability by fusion to protein transduction domains (PTDs). Here, we engineered a universal delivery system based on PTD‐fused Strep‐Tactin, which we named Transtactin. Biochemical characterization of Transtactin variants bearing different PTDs indicated high thermal stabilities and robust secondary structures. Internalization studies demonstrated that Transtactins facilitated simple and safe transport of Strep‐tag II‐linked small molecules, peptides and multicomponent complexes, or biotinylated proteins into cultured human cells. Transtactin‐introduced cargos were functionally active, as shown for horseradish peroxidase serving as a model protein. Our results demonstrate that Transtactin provides a universal and efficient delivery system for Strep‐tag II‐fused cargos. 相似文献
992.
Gene therapy based on gene delivery is a promising strategy for the treatment of various human diseases such as cancer. Cationic lipids represent one of the important synthetic gene delivery systems. There is a great interest in imaging of gene therapy using the biomedical imaging technique positron emission tomography (PET). Carbon-11-labeled cholesterol-based cationic lipids were first designed and synthesized as new potential PET probes for imaging of gene delivery in cancer. The [11C-methyl]quaternary amine target tracers, N-[11C]methyl-N-[4-(cholest-5-en-3β-yloxycarbonyl)butyl]pyrrolidinium iodide ([11C]4a), N-[11C]methyl-N′-[4-(cholest-5-en-3β-yloxycarbonyl)butyl]imidazolium iodide ([11C]4b), N-[11C]methyl-N-[4-(cholest-5-en-3β-yloxycarbonyl)butyl]piperidinium iodide ([11C]4c), N-[11C]methyl-N-[4-(cholest-5-en-3β-yloxycarbonyl)butyl]-4-methylpiperidinium iodide ([11C]4d), and N-[11C]methyl-N-[4-(cholest-5-en-3β-yloxycarbonyl)butyl]morpholinium iodide ([11C]4e), were prepared from their corresponding tertiary amine precursors with [11C]methyl iodide ([11C]CH3I) through N-[11C]methylation and isolated by a simplified solid-phase extraction (SPE) method using a Silica Sep-Pak cartridge in 50-60% radiochemical yields decay corrected to end-of-bombardment (EOB), based on [11C]CO2, and 111-185 GBq/μmol specific activity at the end of synthesis (EOS). 相似文献
993.
Nicole A. Brooks Dodie S. Pouniotis Choon-Kit Tang Vasso Apostolopoulos Geoffrey A. Pietersz 《生物化学与生物物理学报:癌评论》2010
Recent years have seen a surge in interest in cell-penetrating peptides (CPP) as an efficient means for delivering therapeutic targets into cellular compartments. The cell membrane is impermeable to hydrophilic substances yet linking to CPP can facilitate delivery into cells. Thus the unique translocatory property of CPP ensures they remain an attractive carrier, with the capacity to deliver cargoes in an efficient manner having applications in drug delivery, gene transfer and DNA vaccination. Fundamental for an effective vaccine is the delivery of antigen epitopes to antigen-presenting cells, ensuing processing and presentation and induction of an immune response. Vaccination with proteins or synthetic peptides incorporating CTL epitopes have proven limited due to the failure for exogenous antigens to be presented efficiently to T cells. Linking of antigens to CPP overcomes such obstacles by facilitating cellular uptake, processing and presentation of exogenous antigen for the induction of potent immune responses. This review will encompass the various strategies for the delivery of whole proteins, T cell epitopes and preclinical studies utilizing CPP for cancer vaccines. 相似文献
994.
中药透皮吸收促进剂的研究进展 总被引:3,自引:0,他引:3
经皮给药系统(transdermal drug delivery system,TDDS)由于具有超越一般给药方式的独特优点,其研究已经成为第3代药物制剂开发研究的中心内容之一。然而在经皮给药的临床应用中,人们发现,药物的经皮吸收存在着各种障碍,使得药物很难达到预期的有效的治疗效果。近年来,透皮吸收促进剂(penetration enhancers,PE)的应用为经皮给药系统的研究与应用带来了契机,而天然的中药PE以其具有起效快、效果好、副作用小等优点,正日益引起人们的重视,显示出广阔的发展前景。 相似文献
995.
996.
近年来,随着全基因组测序等分子生物技术的应用,人们对阴道微生态系统的结构和功能的认识逐渐清晰。研究发现很多妇科疾病的出现伴随着阴道菌群失调,因此研究正常的阴道菌群结构和功能对预防和治疗菌群失调引起的疾病有重要意义,这也是目前人体微生态研究领域的热点。本文总结了近年关于健康女性阴道菌群的组成和类型的研究,阐述了阴道中常见乳杆菌如卷曲乳杆菌、惰性乳杆菌、格氏乳杆菌、詹氏乳杆菌等在功能研究方面的最新进展,以期为乳杆菌在防治妇科疾病如细菌性阴道病(BV)、外阴假丝酵母菌病(VVC)并推进其产品开发及临床应用等方面提供一些理论参考。 相似文献
997.
目的探讨妊娠期生殖道B族链球菌(GBS)感染患者阴道微生态、血清炎性因子变化及其对母婴结局的影响。方法对482例妊娠妇女的临床资料展开回顾,统计妊娠期生殖道GBS感染情况,并将其分为感染组(GBS细菌培养阳性)和非感染组(GBS细菌培养阴性),其中感染组患者给予抗生素药物治疗。统计妊娠期生殖道GBS感染检出情况;分析并比较感染组与非感染组阴道微生态分布情况;检测感染组与非感染组及感染组治疗前后血清炎性因子的变化情况;统计感染组的治疗效果;分析并比较感染组与非感染组母婴结局情况;分析影响母婴结局的危险因素。结果医院收治的482例妊娠期患者中检出生殖道GBS细菌培养阳性68例,阳性率为14.11%。感染组的阴道微生态环境中GBS、白细胞酯酶、唾液酸酶、乙酰氨基葡萄糖苷酶、脯氨酸氨基肽酶、过氧化氢酶检出率均高于非感染组(均P0.05),阴道菌群密集度II~III度、乳杆菌、清洁度I~II级检出率低于非感染组(均P0.05)。感染组hs-CRP、PCT、IL-6含量均显著高于非感染组(均P0.05),感染组治疗后的C-反应蛋白(hs-CRP)、血清降钙素原(PCT)、白细胞介素-6(IL-6)含量显著低于治疗前(均P0.05)。统计感染组患者的治疗效果及不良事件,其中痊愈57例,好转11例,复发2例。感染组产后出血、宫内感染发生率与与非感染组比,差异无统计学意义(均P0.05),感染组早产、胎膜早破、羊水污染发生率均高于非感染组(均P0.05)。感染组围产儿肺炎、窒息发生率与非感染组比,差异无统计学意义(均P0.05),感染组围产儿宫内窘迫、生理性黄疸发生率均显著高于非感染组(均P0.05);母婴结局发生者高龄产妇、早产、胎膜早破、羊水污染、围产儿宫内窘迫、生理性黄疸、阴道微生态失衡、未抗感染治疗、GBS感染、hs-CRP升高、PCT升高、IL-6升高均高于未发生者(均P0.05),经Logistic回归分析证实均为危险因素(OR=5.540、3.347、6.495、7.036、7.199、5.275、3.093、5.436、5.942、4.683、5.013、5.703,均P0.05)。结论妊娠期生殖道GBS感染患者的阴道微生态菌群改变,血清炎性因子升高,可增加母婴不良结局的发生风险。 相似文献
998.
Sudha Shankar Gurpreet Singh Junaid Ur Rahim Arem Qayum Parduman R. Sharma Meenu Katoch Rajkishor Rai 《Journal of peptide science》2020,26(4-5)
The present work describes the synthesis and characterization of α/γ hybrid peptides, Boc‐Phe‐γ4‐Phe‐Val‐OMe, P1 ; Boc‐Ala‐γ4‐Phe‐Val‐OMe, P2 ; and Boc‐Leu‐γ4‐Phe‐Val‐OMe, P3 together with the formation of self‐assembled structures formed by these hybrid peptides in dimethyl sulfoxide (DMSO)/water (1:1). The self‐assembled structures were characterized by infrared (IR) spectroscopy, circular dichroism (CD), and scanning electron microscopy (SEM). Further, α/γ hybrid peptide self‐assembled structures were evaluated for antibacterial properties. Among all, the self‐assembled peptide P1 exhibited the antimicrobial activity against Escherichia coli and Klebsiella pneumoniae, while self‐assembled peptide P3 inhibited the biofilms of Salmonella typhimurium and Pseudomonas aeruginosa. In this study, we have shown the significance of self‐assembled structures formed from completely hydrophobic α/γ hybrid peptides in exploring the antibacterial properties together with biofilm inhibition. 相似文献
999.
Praveen Kumar Govindaraji Suneetha Vuppu 《Saudi Journal of Biological Sciences》2020,27(12):3529-3540
Pectinases are enzymes which are widely distributed in microbes that are present in pectin enriched sites. The agro-industrial residues can be utilized in the industrial scale for low-cost and efficient pectinase production in an eco-friendly approach. This study employs low-cost substrates (i.e. culinary fruit peels) for maximum pectinase production from novel Streptomyces fumigatiscleroticus VIT-SP4. The extraction and characterization of pectin from different fruit peels were investigated and pectinase activity was analyzed. The orange pectin gave maximum pectinase activity of about 45.93 (U/mL). Further, statistical optimization of process parameters was studied by using Taguchi method showed optimum values of pH-6, temperature −35 °C, orange pectin% − 2.5, incubation time- 48 h and RPM- 200 rpm and pectinase activity was found to be 98.65 (U/mL). The response surface methodology (RSM) was used for the optimization of media components which revealed that starch −1.17%, yeast extract-2%, and orange pectin% − 0.75% produces maximum pectinase of about 170.05 (U/mL). The drug-delivery study showed drug release was not observed at initial pH 3 after 4 h. The immediate drug release was noted at pH 6 caused due to disintegration of pectin by the pectinase activity. The self-healing of cracks by spray culture technique was investigated. The crack healing was observed up to 0.50 mm wide after 12 days. This confirms the ability of actinomycete spores to survive and they react to form calcite complex directly helps in crack healing process. This low-cost microbial pectinase can be used in drug delivery and concrete crack-healing applications sectors in future. 相似文献
1000.