全文获取类型
收费全文 | 2161篇 |
免费 | 136篇 |
出版年
2024年 | 5篇 |
2023年 | 19篇 |
2022年 | 31篇 |
2021年 | 57篇 |
2020年 | 29篇 |
2019年 | 42篇 |
2018年 | 62篇 |
2017年 | 49篇 |
2016年 | 65篇 |
2015年 | 103篇 |
2014年 | 99篇 |
2013年 | 149篇 |
2012年 | 184篇 |
2011年 | 154篇 |
2010年 | 112篇 |
2009年 | 96篇 |
2008年 | 147篇 |
2007年 | 130篇 |
2006年 | 115篇 |
2005年 | 119篇 |
2004年 | 83篇 |
2003年 | 76篇 |
2002年 | 82篇 |
2001年 | 30篇 |
2000年 | 23篇 |
1999年 | 18篇 |
1998年 | 31篇 |
1997年 | 14篇 |
1996年 | 13篇 |
1995年 | 14篇 |
1994年 | 8篇 |
1993年 | 10篇 |
1992年 | 12篇 |
1991年 | 13篇 |
1990年 | 10篇 |
1989年 | 6篇 |
1988年 | 7篇 |
1987年 | 9篇 |
1986年 | 8篇 |
1985年 | 12篇 |
1984年 | 4篇 |
1983年 | 6篇 |
1982年 | 6篇 |
1981年 | 6篇 |
1980年 | 4篇 |
1979年 | 4篇 |
1978年 | 5篇 |
1977年 | 7篇 |
1976年 | 5篇 |
1969年 | 1篇 |
排序方式: 共有2297条查询结果,搜索用时 31 毫秒
971.
Anirban Basu Parasuraman Jaisankar Gopinatha Suresh Kumar 《Molecular biology reports》2014,41(8):5473-5483
Interaction of the 9-O–N-aryl/arylalkyl amino carbonyl methyl substituted analogs of the anticancer isoquinoline alkaloid berberine with RNA triplex, poly(U)-poly(A)·poly(U) has been studied in comparison to the duplex poly(A)-poly(U), using multiple biophysical techniques. Spectrophotometric and spectrofluorimetric studies established the non-cooperative binding mode of all the analogs with both the duplex and the triplex. However, berberine exhibited cooperative binding with poly(A)-poly(U) and non-cooperative binding with poly(U)-poly(A)·poly(U). Analog BER1 showed the highest affinity to both the duplex and the triplex followed by BER2 and BER3. The overall binding affinity varied as BER1 > BER2 > BER3 > BER. The magnitude of the quantum efficiency values (Q > 1) revealed that energy was transferred from the bases of the triplex and the duplex to the analogs. Comparative ferrocyanide quenching and viscosity studies unambiguously established a stronger intercalative geometry of the analogs to both the triplex and the duplex in comparison to berberine. Circular dichroism studies revealed that the alkaloids perturbed the conformation of both RNA helices. The binding of all the alkaloids was found to be exothermic from isothermal titration studies. Binding of the analogs was highly entropy driven while that of berberine was enthalpy dominated. The results presented here reveal strong and specific binding of these new berberine analogs to the RNA triplex and duplex and highlight the remarkable influence of the 9-substitution on the interaction profile. 相似文献
972.
Sireesh Dornadula Suresh Thiruppathi Rajaguru Palanisamy Dhamodharan Umapathy Takayoshi Suzuki Ramkumar K. Mohanram 《Journal of cellular physiology》2019,234(3):1996-2012
Pterostilbene (PTS), a naturally occurring stilbene, confers protection against oxidative and cytokine stress induced pancreatic β-cell apoptosis in vitro and in vivo. To provide insights into the molecular mechanism, we performed a proteomic study on the pancreas of PTS-treated diabetic mice using electrospray ionization tandem–mass spectrometry (LC–MS/MS). A total of 1,260 proteins were detected in triplicate samples. Of which, 359 proteins were found to be differentially regulated in streptozotocin-induced diabetic mice pancreas with two fold difference ( P < 0.05, two or more peptides) and on PTS treatment 315 proteins were normalized to control levels. Gene ontology (GO) indicated that majority of the differentially regulated proteins are involved in cellular functions such as metabolism, cellular structure, oxidative stress, endoplasmic-reticulum-associated protein degradation (ERAD) pathway and several stress sensors. Protein–protein interaction network analysis of these differentially expressed proteins showed clustering of proteins involved in protein processing in endoplasmic reticulum (protein synthesis machinery and protein folding), oxidative phosphorylation/oxidative stress proteins, oligosaccharide metabolic process, and antioxidant activity. Our results highlighted that PTS administration rehabilitated the defective metabolic process and redox imbalance, and also suppressed the unfolded protein response and ERAD pathways. The effects on targeting ER machinery and suppressing oxidative stress suggest the great potential of PTS for diabetes management. 相似文献
973.
975.
976.
Suresh K.A. Palanisamy Carrie Fletcher Livia Tanjung Margaret E. Katz & Brian F. Cheetham 《FEMS microbiology letters》2010,302(1):39-45
The Gram-negative anaerobe Dichelobacter nodosus is the causative agent of footrot in sheep. Different strains of D. nodosus cause disease of differing severities, ranging from benign to virulent. Virulent strains have greater twitching motility and secrete proteases that are more thermostable than those secreted by benign strains. We have identified polynucleotide phosphorylase (PNPase) as a putative virulence regulator and have proposed that PNPase expression is modulated by the adjacent integration of genetic elements. In this study, we compared PNPase activity in three virulent and four benign strains of D. nodosus and found that PNPase activity is lower in virulent strains. We disrupted the pnpA gene in three benign D. nodosus strains and two virulent strains and showed that deletion of the S1 domain of PNPase reduced catalytic activity. In all but one case, deletion of the PNPase S1 domain had no effect on the thermostability of extracellular proteases. However, this deletion resulted in an increase in twitching motility in benign, but not in virulent strains. Reconstruction of the pnpA gene in two mutant benign strains reduced twitching motility to the parental level. These results support the hypothesis that PNPase is a virulence repressor in benign strains of D. nodosus . 相似文献
977.
Subhendu K. Chatterjee Chandan Malick Samir Bhattacharya Vettath R. Suresh Rakesh Kundu Surjya K. Saikia 《Journal of fish biology》2019,95(1):324-334
The chemosensory nature of the tissue from the dorsal surface of the head (also termed sensory pad; SP) of the amphihaline diadromous fish hilsa Tenualosa ilisha was investigated for odorant receptor (OR), olfactory marker protein (OMP) and G-protein subunits (Gαs-olf, Gαq, Gαo, Gαi3) through immunolocalization and immunoblotting techniques. The immunolocalization of OR, OMP and G-protein subunits showed clear expression of these proteins in the tissues of the SP. Robust expressions of these proteins in the SP were detected with immunoblot analysis. The strong expression of these proteins in the SP indicates that the tissues from this area in riverine T. ilisha may play significant role in chemosensing and signalling through ectopic expression of olfactory receptor proteins which are otherwise reported in olfactory organs in vertebrates. Being migratory in nature, ectopic expression of these receptors in T. ilisha probably helps them to prevent damage to epidermal tissues of the SP, or they may also utilize them as a chemo and mechanosensory tool to optimize chemo-communications during migration. 相似文献
978.
Surface potential is a commonly overlooked physical characteristic that plays a dominant role in the adhesion of microorganisms to substrate surfaces. Kelvin probe force microscopy (KPFM) is a module of atomic force microscopy (AFM) that measures the contact potential difference between surfaces at the nano-scale. The combination of KPFM with AFM allows for the simultaneous generation of surface potential and topographical maps of biological samples such as bacterial cells. Here, we employ KPFM to examine the effects of surface potential on microbial adhesion to medically relevant surfaces such as stainless steel and gold. Surface potential maps revealed differences in surface potential for microbial membranes on different material substrates. A step-height graph was generated to show the difference in surface potential at a boundary area between the substrate surface and microorganisms. Changes in cellular membrane surface potential have been linked with changes in cellular metabolism and motility. Therefore, KPFM represents a powerful tool that can be utilized to examine the changes of microbial membrane surface potential upon adhesion to various substrate surfaces. In this study, we demonstrate the procedure to characterize the surface potential of individual methicillin-resistant Staphylococcus aureus USA100 cells on stainless steel and gold using KPFM. 相似文献
979.
Moorthy Suresh 《Inorganica chimica acta》2010,363(12):2881-2885
The emission response of 1-aminopyrene and 2-aminoanthracene was found to be switched ON or OFF by interrupting the Intramolecular Charge Transfer processes of these integrated systems using two binary ionic inputs like H+ or/and OH−. These fluorescence responses in the presence of added H+ or/and OH− could be correlated with Half-subtractor logic operation, revealing the possibility of using simple molecules for demonstrating complex logic operations. 相似文献
980.
Sangeeta Mehta Rakhee Chhetra Radhika Srinivasan Suresh C. Sharma Digambar Behera Sujata Ghosh 《Glycoconjugate journal》2010,27(5):491-500
In this study, we report the presence of significantly higher level of GM3 specific IgG antibodies (IgGTL) in the bronchoalveolar lavage fluid obtained from tumor bearing lung of non-small cell lung cancer (NSCLC) patients as compared
to other non-neoplastic controls. The antibodies were isolated using DEAE-cellulose anion exchange chromatography and molecular
weight of the subunits of IgGTL was confirmed in SDS-PAGE. IgGTL revealed high specificity to GM3 and the IgG distribution was confined to IgG1. Furthermore, IgGTL showed strong reactivity with NSCLC cell lines as well as the tissue biopsies and cells obtained from fine needle aspirations
of NSCLC patients. A 66 kDa membrane glycoprotein of NSCLC cell lines was found to interact specifically with IgGTL, the intensity of which was drastically reduced in presence of GM3. Further, binding of Maackia amurensis agglutinin [specific for NeuAcα(2→3)Gal unit , the same disaccharide unit also known to be present in GM3] to the 66 kDa
band confirmed it to be a sialoglycoprotein in nature. IgGTL could not show any reactivity to alkaline borohydrate treated or periodate oxidised membrane fractions, suggesting the probable
involvement of the carbohydrate moiety of the 66 kDa glycoprotein in the interaction with IgGTL. Thus, the 66 kDa sialoglycoprotein seems to be the NSCLC specific sialoglycoconjugate. Taken together, IgGTL antibodies may have the potential to serve as a unique probe for detail investigation of NSCLC specific cell surface sialoglycoconjugate.
Further, due to high specificity of IgGTL to GM3, it may be possible to develop a simple alternative diagnostic approach (GM3-ELISA) for NSCLC. 相似文献