全文获取类型
收费全文 | 685篇 |
免费 | 43篇 |
国内免费 | 1篇 |
出版年
2023年 | 11篇 |
2022年 | 13篇 |
2021年 | 21篇 |
2020年 | 18篇 |
2019年 | 21篇 |
2018年 | 15篇 |
2017年 | 13篇 |
2016年 | 23篇 |
2015年 | 23篇 |
2014年 | 38篇 |
2013年 | 59篇 |
2012年 | 44篇 |
2011年 | 51篇 |
2010年 | 33篇 |
2009年 | 26篇 |
2008年 | 36篇 |
2007年 | 23篇 |
2006年 | 36篇 |
2005年 | 29篇 |
2004年 | 32篇 |
2003年 | 30篇 |
2002年 | 15篇 |
2001年 | 10篇 |
2000年 | 8篇 |
1999年 | 7篇 |
1998年 | 12篇 |
1997年 | 5篇 |
1996年 | 6篇 |
1995年 | 3篇 |
1994年 | 3篇 |
1993年 | 6篇 |
1992年 | 5篇 |
1991年 | 3篇 |
1990年 | 6篇 |
1989年 | 5篇 |
1988年 | 3篇 |
1987年 | 4篇 |
1986年 | 2篇 |
1985年 | 1篇 |
1984年 | 3篇 |
1982年 | 2篇 |
1981年 | 2篇 |
1980年 | 4篇 |
1979年 | 1篇 |
1978年 | 4篇 |
1977年 | 3篇 |
1976年 | 5篇 |
1975年 | 2篇 |
1973年 | 2篇 |
1972年 | 2篇 |
排序方式: 共有729条查询结果,搜索用时 31 毫秒
721.
We propose a new mathematical modeling framework based on partial differential equations to study tumor virotherapy with mediated immunity. The model incorporates both innate and adaptive immune responses and represents the complex interaction among tumor cells, oncolytic viruses, and immune systems on a domain with a moving boundary. Using carefully designed computational methods, we conduct extensive numerical simulation to the model. The results allow us to examine tumor development under a wide range of settings and provide insight into several important aspects of the virotherapy, including the dependence of the efficacy on a few key parameters and the delay in the adaptive immunity. Our findings also suggest possible ways to improve the virotherapy for tumor treatment. 相似文献
722.
Urinary oestrogen assay and serial ultrasonic cephalometry were performed on 284 patients who were considered on clinical grounds to be at risk of having a growth-retarded fetus. It was found that ultrasonic cephalometry was significantly better than oestrogens in diagnosing the small-for-dates baby, but that there was no significant difference between the two methods in predicting perinatal asphyxia. Of the 14 stillbirths, three were in the normal ultrasonic growth rate group and five had normal oestrogen excretion. Both methods were found to be of value in the diagnosis of fetal growth-retardation, although cephalometry would seem to have some advantages, especially in distinguishing between fetal growth-retardation and mistaken maturity. 相似文献
723.
Asim Raza Dr. Mohsin Abbas Khan Prof. Dr. Irshad Ahmad Dr. Sajid Ur Rehman Dr. Saharish Khaliq Dr. Javed Ahmed Breena Awan Farhat Ullah Anum Masood Naveed Ahmed 《化学与生物多样性》2023,20(7):e202300482
Prodrugs of dexibuprofen having ester moieties instead of free carboxylic acid which involves in gastrointestinal side effects have been synthesized. Dexibuprofen acid was condensed with different alcohols/phenols to afford the ester prodrugs. All of the synthesized prodrugs were characterized by their physical attributes, elemental analysis, FT-IR, 1H-NMR, and 13C-NMR spectroscopy. The in vitro anti-inflammatory studies was done by chemiluminescence technique reflect prodrugs have been more potent, owing to the different chemical structures. Lipoxygenase enzyme inhibition assay was also assess and found compound DR7 with IC50=19.8 μM), DR9 (IC50=24.8 μM) and DR3 (IC50=47.2 μM) as compared with Dexibuprofen (IC50=156.6 μM). It was also evaluated for docking studies revealed that DR7 has found to be more potent anti-inflammatory against 5-LOX (3 V99) as well as analgesic against COX-II (5KIR) enzyme. Anti-oxidant activities were also performed, DR3 (86.9 %), DR5 (83.5 %), DR7 (93.9 %) and DR9 (87.4 %) were found to be more anti-oxidant as compared to (2S)-2-[4-(2-methylpropyl)phenyl]propanoic acid (52.7 %). 相似文献
724.
In the last decade, treatment for castration-resistant prostate cancer has changed markedly, impacting symptom control and longevity for patients. However, a large proportion of cases progress despite androgen deprivation therapy and chemotherapy, while still being fit enough for several more lines of treatment. Overstimulation of the androgen receptor (AR) activity is the main driver of this cancer. Targeting biological functions of the AR or its co-regulators has proven very effective in this disease and led to the development of several highly effective drugs targeting the AR signalling axis. Drugs such as enzalutamide demonstrated that the improvement in anti-tumour efficacy is closely correlated with an affinity for the AR and its activity and have established the paradigm that AR remains activity in aggressive disease. However, as importantly, key insights into mechanisms of resistance are guiding the development of the next generation of AR-targeted drugs. This review outlines the historical development of these highly specific agents, their mechanism of action in the context of defective AR activity, and explores the potential for the upcoming next-generation AR inhibitors (ARI) for prostate cancer by targeting the alternative domains of AR, rather than by the conventional ligand-binding domain approach. There is huge potential in these approaches to develop new drugs with high clinical activity and further improve the outlook for patients. 相似文献
725.
The nitroaromatic explosive 2,4,6-trinitrotoluene (TNT) and the related 2,4-dinitrotoluene (DNT) are toxic environmental pollutants. The biotransformation and detoxication of these persistent compounds in higher organisms are of great significance from a health perspective as well as for the biotechnological challenge of bioremediation of contaminated soil. We demonstrate that different human glutathione transferases (GSTs) and GSTs from the fruit fly Drosophila melanogaster are catalysts of the biotransformation of TNT and DNT. The human GSTs had significant but modest catalytic activities with both DNT and TNT. However, D. melanogaster GSTE6 and GSTE7 displayed outstanding high activities with both substrates. 相似文献
726.
Mark R. Bell Mark J. Engleka Asim Malik James E. Strickler 《Protein science : a publication of the Protein Society》2013,22(11):1466-1477
Since the dawn of time, or at least the dawn of recombinant DNA technology (which for many of today''s scientists is the same thing), investigators have been cloning and expressing heterologous proteins in a variety of different cells for a variety of different reasons. These range from cell biological studies looking at protein-protein interactions, post-translational modifications, and regulation, to laboratory-scale production in support of biochemical, biophysical, and structural studies, to large scale production of potential biotherapeutics. In parallel, fusion-tag technology has grown-up to facilitate microscale purification (pull-downs), protein visualization (epitope tags), enhanced expression and solubility (protein partners, e.g., GST, MBP, TRX, and SUMO), and generic purification (e.g., His-tags, streptag, and FLAG™-tag). Frequently, these latter two goals are combined in a single fusion partner. In this review, we examine the most commonly used fusion methodologies from the perspective of the ultimate use of the tagged protein. That is, what are the most commonly used fusion partners for pull-downs, for structural studies, for production of active proteins, or for large-scale purification? What are the advantages and limitations of each? This review is not meant to be exhaustive and the approach undoubtedly reflects the experiences and interests of the authors. For the sake of brevity, we have largely ignored epitope tags although they receive wide use in cell biology for immunopreciptation. 相似文献
727.
jejunal loops were infused with micellar solutions of cholesterol with or without β-sitostanol (5α-stigmastan-Sβ-ol), and the uptake of 14C-cholesterol by the loop was followed for 20 minutes. It was found that β-sitostanol, given as a ‘solution-mix’ (a solution resulting from the mixture of two separate micellar solutions of cholesterol and β-sitostanol), at a concentration of 0.30 mM reduced cholesterol uptake. Substituting cholesterol for β-sitostanol in the ‘solution-mix’ had no effect on cholesterol uptake by the loop. β-Sitostanol at a concentration of 0.30 mM in the ‘pre-mix” (a solution resulting from pre-mixing of the two sterols prior to preparation of the micellar solution) condition, had no effect on cholesterol absorption. Taken together, these results suggest that the concentration of β-sitostanol-containing micelles is the important factor in its suppression of cholesterol absorption. 相似文献
728.
729.
Pseudomonas sp. 30-3 was enriched from oil-contaminated soil from Wright Valley, Antarctica using JP8 jet fuel as sole carbon source. This isolate exhibited tolerance to temperatures ranging from 0°C to 35°C when cultured in laboratory medium. In a freeze-thaw study, an 89% survival was observed when Pseudomonas sp. 30-3 was exposed to 4°C prior to freezing. PCR amplification of a 248-bp DNA fragment in Pseudomonas sp. 30-3 using capB-gene specific primers showed a 98% amino acid sequence homology with CapB of Pseudomonas fragi and 62% homology with CspA of Escherichia coli. Radiolabeling of total cellular proteins exhibited elevated expression of an 8-kDa protein at 4°C, which suggests that the CapB in Pseudomonas sp. 30-3 may play a pivotal role in survival and tolerance at cold and subzero temperatures. Tolerance to cold temperatures and the ability to degrade hydrocarbons by Pseudomonas sp. 30-3 provide support for the application of bioremediation for petroleum hydrocarbons in Antarctic soils. 相似文献