全文获取类型
收费全文 | 4559篇 |
免费 | 320篇 |
国内免费 | 130篇 |
出版年
2024年 | 3篇 |
2023年 | 65篇 |
2022年 | 88篇 |
2021年 | 145篇 |
2020年 | 184篇 |
2019年 | 236篇 |
2018年 | 226篇 |
2017年 | 157篇 |
2016年 | 148篇 |
2015年 | 142篇 |
2014年 | 393篇 |
2013年 | 463篇 |
2012年 | 297篇 |
2011年 | 391篇 |
2010年 | 295篇 |
2009年 | 243篇 |
2008年 | 252篇 |
2007年 | 218篇 |
2006年 | 187篇 |
2005年 | 165篇 |
2004年 | 125篇 |
2003年 | 96篇 |
2002年 | 116篇 |
2001年 | 58篇 |
2000年 | 32篇 |
1999年 | 32篇 |
1998年 | 23篇 |
1997年 | 28篇 |
1996年 | 16篇 |
1995年 | 12篇 |
1994年 | 18篇 |
1993年 | 13篇 |
1992年 | 14篇 |
1991年 | 17篇 |
1990年 | 9篇 |
1989年 | 7篇 |
1988年 | 7篇 |
1987年 | 4篇 |
1986年 | 5篇 |
1985年 | 4篇 |
1984年 | 15篇 |
1983年 | 17篇 |
1982年 | 9篇 |
1981年 | 10篇 |
1980年 | 6篇 |
1979年 | 5篇 |
1978年 | 2篇 |
1977年 | 2篇 |
1976年 | 4篇 |
1973年 | 2篇 |
排序方式: 共有5009条查询结果,搜索用时 31 毫秒
81.
In recent years, cell-penetrating peptides have proven to be an efficient intracellular delivery system. The mechanism for CPP internalisation, which first involves interaction with the extracellular matrix, is followed in most cases by endocytosis and finally, depending on the type of endocytosis, an intracellular fate is reached. Delivery of cargo attached to a CPP requires endosomal release, for which different methods have recently been proposed. Positively charged amino acids, hydrophobicity and/or amphipathicity are common to CPPs. Moreover, some CPPs can self-assemble. Herein is discussed the role of self assembly in the cellular uptake of CPPs. Sweet Arrow Peptide (SAP) CPP has been shown to aggregate by CD and TEM (freeze-fixation/freeze-drying), although the internalised species have yet to be identified as either the monomer or an aggregate. 相似文献
82.
基于表面等离子共振的新型生物传感技术及其在生命科学中的应用 总被引:5,自引:0,他引:5
生物分子的活性功能是通过分子之间的相互作用来体现的,了解这种相互作用的过程对于生命科学领域的研究及揭示生命发生发展的基本机制具有重要的意义。基于表面等离子共振(surface plasmon resonance,SPR)的新型生物传感技术——BIAcore(biomolecular interaction analysis)是研究生物分子相互作用的理想工具。它可以实时跟踪检测生物分子间结合、解离的整个过程,已被广泛应用于蛋白质组学、信号转导、新药开发、遗传学分析和食品检测等领域,并且显示出广阔的应用前景。 相似文献
83.
为了研究胶质细胞源性神经营养因子(GDNF)在中枢神经系统疾病中的治疗应用,运用基因突变、蛋白质融合表达和蛋白质纯化技术获得分子质量较小的GDNF(△N39)活性片段.将HIV-1 Tat蛋白转导区(protein transduction domain,PTD)的9个碱性氨基酸49RKKRRQRRR57模拟物9个精氨酸(R9)与GDNF(△N39)活性片段融合表达,获得纯度达95%以上的GDNF(△N39)-R9融合蛋白.将GDNF、GDNF(△N39)、GDNF(△N39)-R9分别加入原代培养的中脑多巴胺能神经元和转染GDNF受体GFRαl和Ret的PC12细胞中,观察它们的神经营养活性和毒性.运用脑微血管内皮细胞株B-Endo 3,观察GDNF(△N39)-R9蛋白穿越血管内皮细胞膜的功能;运用脑血管内皮细胞和Matrigel铺板模拟血脑屏障,Transwell法检测Tat-GDNF(△N39)蛋白穿越脑血管内皮细胞和外周胶质膜的能力.结果显示:GDNF(△N39)-R9蛋白具有类似GDNF的神经营养活性,促进原代培养的中脑多巴胺能神经元和稳定表达GFRα1和Ret受体的PC12-GFRα1-Ret细胞株的存活,没有显示毒性,并且能很好地穿过脑微血管内皮细胞层和模拟的血脑屏障. 相似文献
84.
为了研究胶质细胞源性神经营养因子 (GDNF) 在中枢神经系统疾病中的治疗应用,运用基因突变、蛋白质融合表达和蛋白质纯化技术获得分子质量较小的GDNF(ΔN39)活性片段. 将HIV-1 Tat 蛋白转导区 (protein transduction domain,PTD) 的9个碱性氨基酸49RKKRRQRRR57模拟物9个精氨酸(R9)与GDNF(ΔN39)活性片段融合表达,获得纯度达95%以上的GDNF(ΔN39)-R9融合蛋白. 将GDNF、GDNF(ΔN39)、GDNF(ΔN39)-R9分别加入原代培养的中脑多巴胺能神经元和转染GDNF受体GFRα1和Ret的PC12细胞中,观察它们的神经营养活性和毒性. 运用脑微血管内皮细胞株B-Endo 3,观察GDNF(ΔN39)-R9蛋白穿越血管内皮细胞膜的功能;运用脑血管内皮细胞和Matrigel铺板模拟血脑屏障,Transwell法检测Tat-GDNF(ΔN39)蛋白穿越脑血管内皮细胞和外周胶质膜的能力. 结果显示:GDNF(ΔN39)-R9蛋白具有类似GDNF的神经营养活性,促进原代培养的中脑多巴胺能神经元和稳定表达GFRα1和Ret受体的PC12-GFRα1-Ret细胞株的存活,没有显示毒性,并且能很好地穿过脑微血管内皮细胞层和模拟的血脑屏障. 相似文献
85.
183株志贺菌的菌群分布及药敏分析 总被引:3,自引:0,他引:3
陈小丽 《中国微生态学杂志》2006,18(4):315-315,317
目的了解本地区细菌性痢疾菌群分布及药敏情况。方法对183株志贺菌进行菌群分型及药敏分析。结果183株志贺菌有福氏志贺菌168株(91.8%);宋内志贺菌9株(4.9%);痢疾志贺菌4株(2.2%);鲍氏志贺菌2株(1.1%)。药敏试验显示志贺菌对四环素、氨苄西林、复方新诺明耐药严重;对头孢他啶、阿米卡星、诺氟沙星比较敏感。结论本地区志贺菌主要是福氏志贺菌Ⅱa,应根据药敏试验结果选择合适抗菌药物。 相似文献
86.
门诊妇女阴道乳酸菌对临床常用抗生素耐药性的初步研究 总被引:1,自引:0,他引:1
目的研究临床常用抗生素类药物对妇女生殖道正常菌群乳酸菌的影响,为临床医生选用抗生素治疗妇科疾病提供初步参考,并为微生态学治疗和预防相关疾病提供理论依据。方法采用K-B法(纸片扩散法),以临床采集到的12株阴道乳酸菌为试验菌,研究其对临床常用9大类13种抗生素的耐药性。结果在所测试的抗生索中,试验菌对甲硝唑形成的耐药环直径最小,对头孢噻肟形成的耐药直径最大。除甲硝唑外不同菌株对不同抗生索形成的耐药环直径差异较大。结论在该试验的条件下,乳酸菌对甲硝唑耐药性最强,可作为治疗阴道感染的首选药物;乳酸菌对头孢噻肟最敏感,因而在治疗阴道感染时,应尽量避免使用该药物。 相似文献
87.
A series of metallopeptides based on the amino terminal copper/nickel (ATCUN) binding motif have been evaluated as classical inhibitors and catalytic inactivators of both rabbit and human angiotensin-converting enzyme (hACE), and human endothelin-converting enzyme 1 (hECE-1). The cobalt complex [KGHK–Co(NH3)2]2+, where KGHK is lysylglycylhistidyllysine, displayed similar K
I and IC50 values to those found for [KGHK–Cu]+, in spite of the enhanced charge, and so either the influence of charge is offset by the steric influence of the axially coordinated ammine ligands, or binding is dominated by contributions from the amino acid side chains, especially the C-terminal lysine that mimics the binding pattern observed for lisinopril. Moreover, the inhibition observed for [KGHK–Co(NH3)2]2+ contrasts with the activation of hACE by Co2+(aq), reflecting the stimulation of enzyme activity following replacement of the catalytic zinc cofactor by cobalt ion at each of the two active sites. Quantitative analysis of the dose-dependent stimulation of activity by Co2+(aq) yielded apparent affinities of 1.3 ± 0.2 and 56 ± 8 μM for the two sites in the presence of saturating Zn2+ (10 μM). Catalytic inactivation of hACE by [KGHK–Cu] + at subsaturating concentrations had previously been characterized, with k
obs = 2.9 ± 0.5 × 10−2 min−1. Under similar conditions, the same complex is found to catalytically inactivate hECE-1, with k
obs = 2.12 ± 0.16 × 10−2 min−1, demonstrating the potential for dual-action activity against two key drug targets in cardiovascular disease. Irreversible inactivation of a drug target represents a novel mechanism of drug action that complements existing classical inhibitor strategies that underlie current drug discovery efforts.Electronic Supplementary Material Supplementary material is available to authorized users in the online version of this article at . 相似文献
88.
Coating sorghum seeds with Fusarium oxysporum (Foxy 2) for control of the root parasitic weed Striga, appears to be an attractive option for minimizing the inoculum amount, establishing the biocontrol agent in the potential infection zone of the host plants, and offering a simple, easy and economical delivery system. Our investigations resulted in the selection of appropriate seed coating materials and a suitable type and form of fungal inoculum. The coating materials tested were arabic gum (AG10%, 20%, 40%), carboxymethylcellulose (CMC1%, 2%) and pectin (LS 440, LM-5 CS) 1%, while the fungal inoculum included microconidia and fresh and dried chlamydospores produced using different substrates. Foxy 2 survived the seed treatment processing and showed excellent viability on seeds for at least 8 months of storage after coating. In general, the performance of 40% arabic gum in combination with dried chlamydospores was the best among the other types of inoculum and coating material tested. Regardless of the type and form of inoculum and coating materials tested, Foxy 2 was able to colonize all roots, even root tips and hairs of the host (sorghum), thereby meeting important criteria of a promising candidate for controlling Striga when applied as a seed treatment. The efficacy of treated sorghum seed with Foxy 2 using different coating materials in reducing S. hermonthica infestation was evaluated in pot and root chamber trials. Foxy 2 markedly reduced Striga emergence and dry weight and increased the percentage of the diseased emerged Striga shoots. However, the efficacy of seed coating varied according to the type and form of fungal inoculum as well as coating material. Coating sorghum seed with dried chlamydospore inoculum homogenized into 20% arabic gum (as adhesive) showed the highest efficacy of 81 and 77% (i.e., percent reduction in healthy emerged Striga shoots compared to the control treatment) against Striga using either sterilized or non-sterilized soil, respectively. In root chamber bioassays, the application of Foxy 2 in combination with AG40% significantly caused disease in 77% of the germinated Striga seeds and in all tubercles after 25 days of sowing. These findings provide an optimized coating protocol as an attractive delivery system for bioherbicides for root parasitic weeds. 相似文献
89.
毒品快速定量测试方法的探讨 总被引:1,自引:0,他引:1
阐述了毒品金免疫层析试条的定量测试机理,推导出浓度值与吸光度之间的测试模型,并对主要干扰因素及消除方法进行分析。最后验证了毒品快速定量测试方法的可行性。 相似文献
90.
Cyril Rauch Stuart W. Paine Peter Littlewood 《Biochimica et Biophysica Acta (BBA)/General Subjects》2013