全文获取类型
收费全文 | 65411篇 |
免费 | 18083篇 |
国内免费 | 4385篇 |
专业分类
87879篇 |
出版年
2024年 | 122篇 |
2023年 | 488篇 |
2022年 | 1187篇 |
2021年 | 2024篇 |
2020年 | 3228篇 |
2019年 | 5098篇 |
2018年 | 5135篇 |
2017年 | 5155篇 |
2016年 | 5585篇 |
2015年 | 6267篇 |
2014年 | 6567篇 |
2013年 | 7148篇 |
2012年 | 5566篇 |
2011年 | 5056篇 |
2010年 | 5232篇 |
2009年 | 3859篇 |
2008年 | 3139篇 |
2007年 | 2448篇 |
2006年 | 2258篇 |
2005年 | 2080篇 |
2004年 | 1914篇 |
2003年 | 1708篇 |
2002年 | 1509篇 |
2001年 | 1101篇 |
2000年 | 812篇 |
1999年 | 655篇 |
1998年 | 413篇 |
1997年 | 332篇 |
1996年 | 264篇 |
1995年 | 232篇 |
1994年 | 227篇 |
1993年 | 132篇 |
1992年 | 183篇 |
1991年 | 143篇 |
1990年 | 126篇 |
1989年 | 113篇 |
1988年 | 73篇 |
1987年 | 70篇 |
1986年 | 50篇 |
1985年 | 48篇 |
1984年 | 45篇 |
1983年 | 28篇 |
1982年 | 22篇 |
1981年 | 10篇 |
1980年 | 6篇 |
1978年 | 2篇 |
1977年 | 2篇 |
1975年 | 2篇 |
1967年 | 3篇 |
1965年 | 2篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
971.
972.
Sayantani Chatterjee Ling Y. Lee Rebeca Kawahara Jodie L. Abrahams Barbara Adamczyk Merrina Anugraham Christopher Ashwood Zeynep Sumer‐Bayraktar Matthew T. Briggs Jenny H. L. Chik Arun Everest‐Dass Sarah Frster Hannes Hinneburg Katia R. M. Leite Ian Loke Uwe Mginger Edward S. X. Moh Miyako Nakano Saulo Recuero Manveen K. Sethi Miguel Srougi Kathrin Stavenhagen Vignesh Venkatakrishnan Katherine Wongtrakul‐Kish Simone Diestel Peter Hoffmann Niclas G. Karlsson Daniel Kolarich Mark P. Molloy Michael H. Muders Martin K. Oehler Nicolle H. Packer Giuseppe Palmisano Morten Thaysen‐Andersen 《Proteomics》2019,19(21-22)
While aberrant protein glycosylation is a recognized characteristic of human cancers, advances in glycoanalytics continue to discover new associations between glycoproteins and tumorigenesis. This glycomics‐centric study investigates a possible link between protein paucimannosylation, an under‐studied class of human N‐glycosylation [Man1‐3GlcNAc2Fuc0‐1], and cancer. The paucimannosidic glycans (PMGs) of 34 cancer cell lines and 133 tissue samples spanning 11 cancer types and matching non‐cancerous specimens are profiled from 467 published and unpublished PGC‐LC‐MS/MS N‐glycome datasets collected over a decade. PMGs, particularly Man2‐3GlcNAc2Fuc1, are prominent features of 29 cancer cell lines, but the PMG level varies dramatically across and within the cancer types (1.0–50.2%). Analyses of paired (tumor/non‐tumor) and stage‐stratified tissues demonstrate that PMGs are significantly enriched in tumor tissues from several cancer types including liver cancer (p = 0.0033) and colorectal cancer (p = 0.0017) and is elevated as a result of prostate cancer and chronic lymphocytic leukaemia progression (p < 0.05). Surface expression of paucimannosidic epitopes is demonstrated on human glioblastoma cells using immunofluorescence while biosynthetic involvement of N‐acetyl‐β‐hexosaminidase is indicated by quantitative proteomics. This intriguing association between protein paucimannosylation and human cancers warrants further exploration to detail the biosynthesis, cellular location(s), protein carriers, and functions of paucimannosylation in tumorigenesis and metastasis. 相似文献
973.
974.
975.
In vitro and in vivo characterization of an interleukin‐15 antagonist peptide by metabolic stability, 99mTc‐labeling,and biological activity assays 下载免费PDF全文
Yunier Rodríguez‐Álvarez Ania Cabrales‐Rico Alejandro Perera‐Pintado Anais Prats‐Capote Hilda E. Garay‐Pérez Osvaldo Reyes‐Acosta Erik Pérez‐García Araceli Chico‐Capote Alicia Santos‐Savio 《Journal of peptide science》2018,24(4-5)
Interleukin (IL)–15 is an inflammatory cytokine that constitutes a validated therapeutic target in some immunopathologies, including rheumatoid arthritis (RA). Previously, we identified an IL‐15 antagonist peptide named [K6T]P8, with potential therapeutic application in RA. In the current work, the metabolic stability of this peptide in synovial fluids from RA patients was studied. Moreover, [K6T]P8 peptide was labeled with 99mTc to investigate its stability in human plasma and its biodistribution pattern in healthy rats. The biological activity of [K6T]P8 peptide and its dimer was evaluated in CTLL‐2 cells, using 3 different additives to improve the solubility of these peptides. The half‐life of [K6T]P8 in human synovial fluid was 5.88 ± 1.73 minutes, and the major chemical modifications included peptide dimerization, cysteinylation, and methionine oxidation. Radiolabeling of [K6T]P8 with 99mTc showed a yield of approximately 99.8%. The 99mTc‐labeled peptide was stable in a 30‐fold molar excess of cysteine and in human plasma, displaying a low affinity to plasma proteins. Preliminary biodistribution studies in healthy Wistar rats suggested a slow elimination of the peptide through the renal and hepatic pathways. Although citric acid, sucrose, and Tween 80 enhanced the solubility of [K6T]P8 peptide and its dimer, only the sucrose did not interfere with the in vitro proliferation assay used to assess their biological activity. The results here presented, reinforce nonclinical characterization of the [K6T]P8 peptide, a potential agent for the treatment of RA and other diseases associated with IL‐15 overexpression. 相似文献
976.
Hitoshi Ando Hayato Yanagihara Koh‐ichi Sugimoto Yohei Hayashi Shuichi Tsuruoka Toshinari Takamura 《Chronobiology international》2013,30(4):655-665
Recent studies have shown the gene expression of several transporters to be circadian rhythmic. However, it remains to be elucidated whether the expression of P‐glycoprotein, which is involved in the transport of many medications, undergoes 24 h rhythmicity. To address this issue, we investigated daily profiles of P‐glycoprotein mRNA and protein levels in peripheral mouse tissues. In the liver and intestine, but not in the kidney, Abcb1a mRNA expression showed clear 24 h rhythmicity. On the other hand, Abcb1b and Abcb4, the other P‐glycoprotein genes, did not exhibit significant rhythmic expression in the studied tissues. In the intestine, levels of whole P‐glycoprotein also exhibited a daily rhythm, with a peak occurring in the latter half of the light phase and a trough at the onset of the light phase. Consistent with the day‐night change of P‐glycoprotein level, the ex vivo accumulation of digoxin, an Abcb1a P‐glycoprotein substrate, into the intestinal segments at the onset of dark phase was significantly lower than it was at the onset of the light phase. Thus, Abcb1a P‐glycoprotein expression, and apparently its function, are 24 h rhythmic at least in mouse intestine tissue. This circadian variation might be involved in various chronopharmacological phenomena. 相似文献
977.
多功能降解菌Pseudomonas putida KT2440-DOP的构建与降解特性研究 总被引:2,自引:0,他引:2
三唑磷水解酶基因为研究发现的一个新的广谱有机磷水解酶基因,通过PCR从有机磷降解菌株Ochrobactrumsp.mp-4总DNA扩增了tpd,将tpd定向克隆到pBBRMCS-5载体上,构建重组质粒pTPD,在辅助质粒pRK2013的帮助下,通过三亲接合将pTPD转移到模式菌株Pseudomonas putidaKT2440中,获得的工程菌PseudomonasputidaKT2440-DOP可以降解多种有机磷农药及芳香烃化合物;KT2440-DOP的有机磷水解酶活较出发菌株MP-4提高了一倍左右,且遗传性状稳定。 相似文献
978.
979.
目的了解不同温度条件对马免疫血浆外观和效价的稳定性影响,为马免疫血浆的采集、分离、贮存、运输及抗毒素生产提供数据支持。方法将破伤风类毒素及肉毒A、B、E、F型类毒素制备的马免疫血浆,分别放置于2~8℃、20℃、37℃3种温度下,并分别于0、1、3、6、12个月取样,依据《中国药典》三部(2010版)的检测方法和标准,对样品进行外观检查及效价检测。结果破伤风及肉毒A、B、E、F型马免疫血浆在2~8℃条件下,放置12个月稳定性良好,外观及效价均符合《中国药典》三部(2010版)规定要求。20℃与37℃下放置的马免疫血浆随着时间的延长,外观会发生不同程度的浑浊,效价也均有不同程度的降低,低效价组比中、高效价组的效价下降明显,且温度越高效价降低幅度越大。结论马免疫血浆在2~8℃条件下质量稳定。 相似文献
980.