全文获取类型
收费全文 | 797篇 |
免费 | 57篇 |
国内免费 | 43篇 |
出版年
2024年 | 3篇 |
2023年 | 11篇 |
2022年 | 21篇 |
2021年 | 47篇 |
2020年 | 26篇 |
2019年 | 24篇 |
2018年 | 42篇 |
2017年 | 27篇 |
2016年 | 33篇 |
2015年 | 40篇 |
2014年 | 58篇 |
2013年 | 61篇 |
2012年 | 77篇 |
2011年 | 66篇 |
2010年 | 42篇 |
2009年 | 35篇 |
2008年 | 34篇 |
2007年 | 31篇 |
2006年 | 29篇 |
2005年 | 24篇 |
2004年 | 20篇 |
2003年 | 22篇 |
2002年 | 24篇 |
2001年 | 17篇 |
2000年 | 15篇 |
1999年 | 3篇 |
1998年 | 3篇 |
1997年 | 3篇 |
1996年 | 4篇 |
1995年 | 4篇 |
1994年 | 4篇 |
1993年 | 6篇 |
1992年 | 5篇 |
1991年 | 7篇 |
1990年 | 1篇 |
1989年 | 6篇 |
1988年 | 1篇 |
1987年 | 3篇 |
1986年 | 3篇 |
1984年 | 3篇 |
1982年 | 2篇 |
1981年 | 3篇 |
1977年 | 2篇 |
1976年 | 2篇 |
1971年 | 1篇 |
1970年 | 1篇 |
1950年 | 1篇 |
排序方式: 共有897条查询结果,搜索用时 15 毫秒
151.
Protein p63 is a key regulator in cell proliferation and cell differentiation in stratified squamous epithelium. ΔNp63α is the most commonly expressed p63 isoform, which is often overexpressed in human tumor. In the present work we report the potential involvement of ΔNp63α in cell cycle regulation. ΔNp63α accumulated in mitotic cells but its expression decreased during mitotic exit. Moreover, ΔNp63α knockdown promoted mitotic exit. ΔNp63α shares a conserved destruction box (D-box) motif with other potential targets of the Anaphase-Promoting Complex/Cyclosome (APC/C). Overexpression of APC/C coactivator Cdh1 destabilized ΔNp63α. Our results suggest that ΔNp63α level is cell cycle-regulated and may play a role in the regulation of mitotic exit. 相似文献
152.
Hu S Ni W Sai W Zhang H Cao X Qiao J Sheng J Guo F Chen C 《Biotechnology letters》2011,33(10):1949-1953
Myostatin is a negative regulator of skeletal muscle growth. Myostatin dysfunction therefore offers a strategy for promoting
animal muscle growth in livestock production. Knockdown of myostatin was achieved by combining RNA interference and the Sleeping
Beauty (SB) transposon system in sheep cells. Four targeting sites of sheep myostatin were designed and measured for myostatin
silencing in sheep fetal fibroblasts by real-time PCR. The sh3 construct induced significant decrease of myostatin gene expression
by 90% (P < 0.05). Myostatin silencing induced by SB-mediated sh3 was further tested in stably transfected cells. SB transposition
increased the integration frequency of genes into sheep genomes and mediated a more efficient myostatin knockdown than random
integration of sh3. We suggest that SB-mediated shRNA provides a novel potential tool for gene knockdown in the donor cells
of animal cloning. 相似文献
153.
Li D Zhao B Sim SP Li TK Liu A Liu LF LaVoie EJ 《Bioorganic & medicinal chemistry》2003,11(4):521-528
Appropriately substituted benzo[i]phenanthridines structurally related to nitidine, a benzo[c]phenanthridine alkaloid with antitumor activity, are active as topoisomerase I-targeting agents. Studies on benzo[i]phenanthridines have indicated analogues that possess a 2,3-methylenedioxy moiety and at least one and preferably two methoxyl groups at the 8- and 9-positions, such as 8,9-dimethoxy-2,3-methylenedioxybenzo[i]phenanthridine, 2, are active as topoisomerase I-targeting agents. Tetramethoxylated benzo[i]phenanthridines, wherein the 2,3-methylenedioxy moiety is replaced with methoxyl groups at the 2- and 3-position, are inactive as a topoisomerase I-targeting agent. These results initially suggested that the 2,3-methylenedioxy moiety was critical to the retention of potent activity. Further studies revealed that 2,3-dimethoxy-8,9-methylenedioxybenzo[i]phenanthridine, 7a, is more potent than 2 as a topoisomerase I-targeting agent. The observation that 2,3-dimethoxylated benzo[i]phenanthridines can actually exhibit enhanced activity prompted the present study in which several 8-substituted 2,3-dimethoxybenzo[i]phenanthridines were prepared and their pharmacological activities evaluated. The influence of NH(2), CN, CH(2)OH, OBn, OCH(3), OH, and NHCOCH(3 )substituents at the 8-position on the relative activity of these 2,3-dimethoxybenzo[i]phenanthridines was examined. Relative to these derivatives, 7a was the most potent topoisomerase I-targeting agent, possessing similar cytotoxicity to that of nitidine in the human lymphoblast tumor cell line, RPMI8402. 相似文献
154.
Batch‐to‐Batch Variation of Polymeric Photovoltaic Materials: its Origin and Impacts on Charge Carrier Transport and Device Performances
下载免费PDF全文
![点击此处可从《Liver Transplantation》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Harrison Ka Hin Lee Zhao Li Iordania Constantinou Franky So Sai Wing Tsang Shu Kong So 《Liver Transplantation》2014,4(16)
A detailed investigation of the impact of molecular weight distribution of a photoactive polymer, poly[N‐9′‐heptadecanyl‐2,7‐carbazole‐alt‐5,5‐(4′,7′‐di‐2‐thienyl‐2′,1′,3′‐benzothiadiazole)] (PCDTBT), on photovoltaic device performance and carrier transport properties is reported. It is found that different batches of as‐received polymers have substantial differences in their molecular weight distribution. As revealed by gel permeation chromatography (GPC), two peaks can generally be observed. One of the peaks corresponds to a high molecular weight component and the other peak corresponds to a low molecular weight component. Photovoltaic devices fabricated with a higher proportion of low molecular weight component have power conversion efficiencies (PCEs) reduced from 5.7% to 2.5%. The corresponding charge carrier mobility at the short‐circuit region is also significantly reduced from 2.7 × 10?5 to 1.6 × 10?8 cm2 V?1 s?1. The carrier transport properties of the polymers at various temperatures are further analyzed by the Gaussian disorder model (GDM). All polymers have similar energetic disorders. However, they appear to have significant differences in carrier hopping distances. This result provides insight into the origin of the molecular weight effect on carrier transport in polymeric semiconducting materials. 相似文献
155.
Optoelectronic Devices: Low‐Temperature Combustion‐Synthesized Nickel Oxide Thin Films as Hole‐Transport Interlayers for Solution‐Processed Optoelectronic Devices (Adv. Energy Mater. 6/2014)
下载免费PDF全文
![点击此处可从《Liver Transplantation》网站下载免费的PDF全文](/ch/ext_images/free.gif)
156.
Sai Zou Lei Wang Junfeng Wang 《EURASIP Journal on Bioinformatics and Systems Biology》2014,2014(1):1-7
In this paper, we first present a new concept of ‘weight’ for 64 triplets and define a different weight for each kind of triplet. Then, we give a novel 2D graphical representation for DNA sequences, which can transform a DNA sequence into a plot set to facilitate quantitative comparisons of DNA sequences. Thereafter, associating with a newly designed measure of similarity, we introduce a novel approach to make similarities/dissimilarities analysis of DNA sequences. Finally, the applications in similarities/dissimilarities analysis of the complete coding sequences of β-globin genes of 11 species illustrate the utilities of our newly proposed method. 相似文献
157.
Meghavi N. Patel Sushant Lakkadwala Mohamed S. Majrad Elisha R. Injeti Steven M. Gollmer Zahoor A. Shah Sai Hanuman Sagar Boddu Jerry Nesamony 《AAPS PharmSciTech》2014,15(6):1498-1508
The aim of this research was to advance solid lipid nanoparticle (SLN) preparation methodology by preparing glyceryl monostearate (GMS) nanoparticles using a temperature-modulated solidification process. The technique was reproducible and prepared nanoparticles without the need of organic solvents. An anticancer agent, 5-fluorouracil (5-FU), was incorporated in the SLNs. The SLNs were characterized by particle size analysis, zeta potential analysis, differential scanning calorimetry (DSC), infrared spectroscopy, atomic force microscopy (AFM), transmission electron microscopy (TEM), drug encapsulation efficiency, in vitro drug release, and in vitro cell viability studies. Particle size of the SLN dispersion was below 100 nm, and that of redispersed lyophilizates was ~500 nm. DSC and infrared spectroscopy suggested that the degree of crystallinity did not decrease appreciably when compared to GMS. TEM and AFM images showed well-defined spherical to oval particles. The drug encapsulation efficiency was found to be approximately 46%. In vitro drug release studies showed that 80% of the encapsulated drug was released within 1 h. In vitro cell cultures were biocompatible with blank SLNs but demonstrated concentration-dependent changes in cell viability to 5-FU-loaded SLNs. The 5-FU-loaded SLNs can potentially be utilized in an anticancer drug delivery system.KEY WORDS: atomic force microscopy, calorimetry (DSC), FTIR, particle size, solid lipid nanoparticles 相似文献
158.
Sai S. Sagiri Kunal Pal Piyali Basak Usman Ali Rana Imran Shakir Arfat Anis 《AAPS PharmSciTech》2014,15(5):1197-1208
Leaching of the internal apolar phase from the biopolymeric microparticles during storage is a great concern as it undoes the beneficial effects of encapsulation. In this paper, a novel formulation was prepared by encapsulating the sunflower oil-based organogels in alginate microparticles. Salicylic acid and metronidazole were used as the model drugs. The microparticles were prepared by double emulsion methodology. Physico-chemical characterization of the microparticles was done by microscopy, FTIR, XRD, and DSC studies. Oil leaching studies, biocompatibility, mucoadhesivity, in vitro drug release, and the antimicrobial efficiency of the microparticles were also performed. The microparticles were found to be spherical in shape. Gelation of the sunflower oil prevented leaching of the internal phase from the microparticles. Release of drugs from the microparticles followed Fickian kinetics and non-Fickian kinetics in gastric and intestinal environments, respectively. Microparticles showed good antimicrobial activity against both Gram-positive (Bacillus subtilis) and Gram-negative (Escherichia coli) bacteria. The results suggested that the developed formulations hold promise to carry oils without leakage of the internal phase. Encapsulation of organogels within the microparticles has improved the drug entrapment efficiency and improved characteristics for controlled delivery applications.
Electronic supplementary material
The online version of this article (doi:10.1208/s12249-014-0147-2) contains supplementary material, which is available to authorized users.KEY WORDS: alginate, drug delivery, leaching, microparticles, organogels 相似文献159.
Ulrike Menzel Victor Greiff Tarik A. Khan Ulrike Haessler Ina Hellmann Simon Friedensohn Skylar C. Cook Mark Pogson Sai T. Reddy 《PloS one》2014,9(5)
High-throughput sequencing (HTS) of antibody repertoire libraries has become a powerful tool in the field of systems immunology. However, numerous sources of bias in HTS workflows may affect the obtained antibody repertoire data. A crucial step in antibody library preparation is the addition of short platform-specific nucleotide adapter sequences. As of yet, the impact of the method of adapter addition on experimental library preparation and the resulting antibody repertoire HTS datasets has not been thoroughly investigated. Therefore, we compared three standard library preparation methods by performing Illumina HTS on antibody variable heavy genes from murine antibody-secreting cells. Clonal overlap and rank statistics demonstrated that the investigated methods produced equivalent HTS datasets. PCR-based methods were experimentally superior to ligation with respect to speed, efficiency, and practicality. Finally, using a two-step PCR based method we established a protocol for antibody repertoire library generation, beginning from inputs as low as 1 ng of total RNA. In summary, this study represents a major advance towards a standardized experimental framework for antibody HTS, thus opening up the potential for systems-based, cross-experiment meta-analyses of antibody repertoires. 相似文献
160.
Jasbir D. Upadhyaya Nisha Singh Anurag S. Sikarwar Raja Chakraborty Sai P. Pydi Rajinder P. Bhullar Shyamala Dakshinamurti Prashen Chelikani 《PloS one》2014,9(10)
Activation of bitter taste receptors (T2Rs) in human airway smooth muscle cells leads to muscle relaxation and bronchodilation. This finding led to our hypothesis that T2Rs are expressed in human pulmonary artery smooth muscle cells and might be involved in regulating the vascular tone. RT-PCR was performed to reveal the expression of T2Rs in human pulmonary artery smooth muscle cells. Of the 25 T2Rs, 21 were expressed in these cells. Functional characterization was done by calcium imaging after stimulating the cells with different bitter agonists. Increased calcium responses were observed with most of the agonists, the largest increase seen for dextromethorphan. Previously in site-directed mutational studies, we have characterized the response of T2R1 to dextromethorphan, therefore, T2R1 was selected for further analysis in this study. Knockdown with T2R1 specific shRNA decreased mRNA levels, protein levels and dextromethorphan-induced calcium responses in pulmonary artery smooth muscle cells by up to 50%. To analyze if T2Rs are involved in regulating the pulmonary vascular tone, ex vivo studies using pulmonary arterial and airway rings were pursued. Myographic studies using porcine pulmonary arterial and airway rings showed that stimulation with dextromethorphan led to contraction of the pulmonary arterial and relaxation of the airway rings. This study shows that dextromethorphan, acting through T2R1, causes vasoconstrictor responses in the pulmonary circuit and relaxation in the airways. 相似文献