全文获取类型
收费全文 | 1056篇 |
免费 | 115篇 |
国内免费 | 34篇 |
专业分类
1205篇 |
出版年
2023年 | 21篇 |
2022年 | 25篇 |
2021年 | 56篇 |
2020年 | 42篇 |
2019年 | 63篇 |
2018年 | 56篇 |
2017年 | 39篇 |
2016年 | 44篇 |
2015年 | 48篇 |
2014年 | 58篇 |
2013年 | 83篇 |
2012年 | 66篇 |
2011年 | 51篇 |
2010年 | 49篇 |
2009年 | 51篇 |
2008年 | 58篇 |
2007年 | 61篇 |
2006年 | 45篇 |
2005年 | 39篇 |
2004年 | 23篇 |
2003年 | 19篇 |
2002年 | 31篇 |
2001年 | 16篇 |
2000年 | 17篇 |
1999年 | 13篇 |
1998年 | 10篇 |
1997年 | 13篇 |
1996年 | 15篇 |
1995年 | 4篇 |
1994年 | 15篇 |
1993年 | 12篇 |
1992年 | 5篇 |
1991年 | 9篇 |
1990年 | 8篇 |
1989年 | 5篇 |
1988年 | 4篇 |
1987年 | 4篇 |
1986年 | 4篇 |
1985年 | 7篇 |
1984年 | 7篇 |
1983年 | 1篇 |
1982年 | 2篇 |
1981年 | 4篇 |
1980年 | 1篇 |
1977年 | 1篇 |
排序方式: 共有1205条查询结果,搜索用时 15 毫秒
61.
Liya Ming Yang Zou Yiming Zhao Luna Zhang Ningning He Zhen Chen Shawn S.‐C. Li Lei Li 《Proteomics》2020,20(15-16)
A large number of post‐translational modifications (PTMs) in proteins are buried in the unassigned mass spectrometric (MS) spectra in shot‐gun proteomics datasets. Because the modified peptide fragments are low in abundance relative to the corresponding non‐modified versions, it is critical to develop tools that allow facile evaluation of assignment of PTMs based on the MS/MS spectra. Such tools will preferably have the ability to allow comparison of fragment ion spectra and retention time between the modified and unmodified peptide pairs or group. Herein, MMS2plot, an R package for visualizing peptide‐spectrum matches (PSMs) for multiple peptides, is described. MMS2plot features a batch mode and generates the output images in vector graphics file format that facilitate evaluation and publication of the PSM assignment. MMS2plot is expected to play an important role in PTM discovery from large‐scale proteomics datasets generated by liquid chromatography‐MS/MS. The MMS2plot package is freely available at https://github.com/lileir/MMS2plot under the GPL‐3 license. 相似文献
62.
63.
64.
65.
Mitochondrial function and autophagy: integrating proteotoxic,redox, and metabolic stress in Parkinson's disease 下载免费PDF全文
Jianhua Zhang Matilda Lillian Culp Jason G. Craver Victor Darley‐Usmar 《Journal of neurochemistry》2018,144(6):691-709
Parkinson's disease (PD) is a movement disorder with widespread neurodegeneration in the brain. Significant oxidative, reductive, metabolic, and proteotoxic alterations have been observed in PD postmortem brains. The alterations of mitochondrial function resulting in decreased bioenergetic health is important and needs to be further examined to help develop biomarkers for PD severity and prognosis. It is now becoming clear that multiple hits on metabolic and signaling pathways are likely to exacerbate PD pathogenesis. Indeed, data obtained from genetic and genome association studies have implicated interactive contributions of genes controlling protein quality control and metabolism. For example, loss of key proteins that are responsible for clearance of dysfunctional mitochondria through a process called mitophagy has been found to cause PD, and a significant proportion of genes associated with PD encode proteins involved in the autophagy‐lysosomal pathway. In this review, we highlight the evidence for the targeting of mitochondria by proteotoxic, redox and metabolic stress, and the role autophagic surveillance in maintenance of mitochondrial quality. Furthermore, we summarize the role of α‐synuclein, leucine‐rich repeat kinase 2, and tau in modulating mitochondrial function and autophagy. Among the stressors that can overwhelm the mitochondrial quality control mechanisms, we will discuss 4‐hydroxynonenal and nitric oxide. The impact of autophagy is context depend and as such can have both beneficial and detrimental effects. Furthermore, we highlight the potential of targeting mitochondria and autophagic function as an integrated therapeutic strategy and the emerging contribution of the microbiome to PD susceptibility.
66.
Carole L. Harker Philip M. Mullineaux John A. Bryant Andrew J. Maule 《Plant molecular biology》1987,8(3):275-287
Specific antisera were prepared to the inclusion body protein (gene VI product) and the gene I product of cauliflower mosaic virus (CaMV). Translational fusions between the lacZ gene and gene VI or gene I were constructed by cloning the relevant DNA fragments into the expression vectors pUR290, pUR291 or pUR292. Large amounts of fusion protein were synthesized when the inserted DNA fragment was in frame with the lacZ gene of the expression vector. These fusion proteins were used to raise specific antisera to gene VI and gene I proteins of CaMV. Antiserum to the gene VI product detected a range of proteins in crude extracts and in a subcellular fraction enriched for virus inclusion bodies. This range of proteins was further shown to be related to gene VI by Staphylococcus aureus V8 partial proteolysis. Antiserum to the gene I product detected viral specific proteins of 46, 42 and 38 K in preparations of CaMV replication complexes from infected plants but not in any other subcellular fraction. 相似文献
67.
Gerbrand J. van der Heden van Noort Catherine H. Schein Herman S. Overkleeft Gijsbert A. van der Marel Dmitri V. Filippov 《Journal of peptide science》2013,19(6):333-336
Small proteins called viral protein genome‐linked (VPg), attached to the 5′‐end of the viral RNA genome are found as common structure in the large family of picornaviruses. The replication of these viruses is primed by this VPg protein linked to a single uridylyl residue. We report a general procedure to obtain such nucleoproteins employing a pre‐uridylylated tyrosine building block in an on‐line solid phase‐based approach. Copyright © 2013 European Peptide Society and John Wiley & Sons, Ltd. 相似文献
68.
Isabel Figueroa Doug Leipold Steve Leong Bing Zheng Montserrat Triguero-Carrasco Aimee Fourie-O'Donohue 《MABS-AUSTIN》2018,10(5):738-750
For antibody-drug conjugates (ADCs) that carry a cytotoxic drug, doses that can be administered in preclinical studies are typically limited by tolerability, leading to a narrow dose range that can be tested. For molecules with non-linear pharmacokinetics (PK), this limited dose range may be insufficient to fully characterize the PK of the ADC and limits translation to humans. Mathematical PK models are frequently used for molecule selection during preclinical drug development and for translational predictions to guide clinical study design. Here, we present a practical approach that uses limited PK and receptor occupancy (RO) data of the corresponding unconjugated antibody to predict ADC PK when conjugation does not alter the non-specific clearance or the antibody-target interaction. We used a 2-compartment model incorporating non-specific and specific (target mediated) clearances, where the latter is a function of RO, to describe the PK of anti-CD33 ADC with dose-limiting neutropenia in cynomolgus monkeys. We tested our model by comparing PK predictions based on the unconjugated antibody to observed ADC PK data that was not utilized for model development. Prospective prediction of human PK was performed by incorporating in vitro binding affinity differences between species for varying levels of CD33 target expression. Additionally, this approach was used to predict human PK of other previously tested anti-CD33 molecules with published clinical data. The findings showed that, for a cytotoxic ADC with non-linear PK and limited preclinical PK data, incorporating RO in the PK model and using data from the corresponding unconjugated antibody at higher doses allowed the identification of parameters to characterize monkey PK and enabled human PK predictions. 相似文献
69.
70.