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排序方式: 共有436条查询结果,搜索用时 15 毫秒
41.
C. Ratna Prabha Soumya Mukherjee Renuka Raman Swapnali Kulkarni 《Applied microbiology and biotechnology》2012,96(5):1111-1123
Studies on knockout mutants and conditional mutants are invaluable to biological research and have been used extensively to probe the intricacies of biological systems through loss of function associated with attenuation of a particular protein. Besides, RNAi technology has been developed in recent years to further aid the process of scientific inquiry. Even though, the methods, dealing with DNA and RNA have met with great success, are not without their shortcomings. In order to overcome the inadequacies of existing methods, a host of new techniques, aimed at knockdowns at the protein rather than the nucleic acid level, have been devised. Essentially, these methods can achieve rapid degradation of cellular pools of a target protein in response to an inducible signal coupled with dose-dependent modulation and exquisite temporal control, features which are absent from techniques involving manipulations at the DNA or RNA level. This review aims to provide a broad overview of a gamut of these methods, while highlighting the strengths and weaknesses of each one. Last two decades of advances presented here in the field of targeted protein degradation serve as a beacon to further research and are likely to find applications in the areas of medicine and allied fields of biology. 相似文献
42.
43.
S El Abed SK Ibnsouda H Latrache H Meftah NJ Tahri F Hamadi 《World journal of microbiology & biotechnology》2012,28(4):1707-1713
Initial microbial adhesion to surfaces is a complicated process that is affected by a number of factors. An important property of a solution that may influence adhesion is pH. The surface properties of the cedar wood were characterized by the sessile drop technique. Moreover, the interfacial free energy of surface adhesion to the cedar wood was determined under pH values (2, 3, 5, 7, 9 and 11). The results showed that cedar wood examined at different pH levels could be considered hydrophobic ranged from Giwi = ?13.1 mJ/m2 to Giwi = ?75 mJ/m2. We noted that the electron-donor character of cedar wood was important at both basic and limit acidic conditions (pH 11 and pH 3) and it decreased at intermediate pH (pH 5). The cedar wood substratum presents a weak electron acceptor under various pH’s. In addition, the adhesion of conidia from Penicilllium expansum to the cedar wood surfaces at different pH values (2, 3, 5, 7, 9 and 11) was investigated using Environmental Scanning Electron Microscopy and image analysis was assessed with the Mathlab® program. The data analysis showed that the conidia from P. expansum were strongly influenced by the pH. The maximum adhesion occurs in the pH 11 and pH 3 and decreased to 24% at pH 5. 相似文献
44.
Karoli T Mamidyala SK Zuegg J Fry SR Tee EH Bradford TA Madala PK Huang JX Ramu S Butler MS Cooper MA 《Bioorganic & medicinal chemistry letters》2012,22(7):2428-2433
The rise of antibiotic resistance is of great clinical concern. One approach to reducing the development of resistance is to co-administer two or more antibiotics with different modes of action. However, it can be difficult to control the distribution and pharmacokinetics of two drugs to ensure both concentrations remain within the range of therapeutic efficacy whilst avoiding adverse effects. Hybrid drugs, where two drugs are linked together with a flexible linker, have been explored, but the resultant large, flexible molecules can have poor bioavailability. We have developed a chimeric approach using click chemistry where the pharmacophores of two drugs are overlapped into a single smaller, more drug-like molecule. Design and selection of compounds were assisted by in silico structural docking. We prepared a series of compounds that include candidates showing activity against the targets of both trimethoprim; dihydrofolate reductase, and ciprofloxacin; DNA gyrase and topoisomerase IV. The resultant triazole containing molecules show modest, but broad spectrum activities against drug sensitive and resistant Gram-negative and Gram-positive bacteria, with no observable cytotoxicity. 相似文献
45.
Kirubakaran S Gorla SK Sharling L Zhang M Liu X Ray SS Macpherson IS Striepen B Hedstrom L Cuny GD 《Bioorganic & medicinal chemistry letters》2012,22(5):1985-1988
Cryptosporidium parasites are important waterborne pathogens of both humans and animals. The Cryptosporidium parvum and Cryptosporidium hominis genomes indicate that the only route to guanine nucleotides is via inosine 5'-monophosphate dehydrogenase (IMPDH). Thus the inhibition of the parasite IMPDH presents a potential strategy for treating Cryptosporidium infections. A selective benzimidazole-based inhibitor of C. parvum IMPDH (CpIMPDH) was previously identified in a high throughput screen. Here we report a structure-activity relationship study of benzimidazole-based compounds that resulted in potent and selective inhibitors of CpIMPDH. Several compounds display potent antiparasitic activity in vitro. 相似文献
46.
OW Kwon E Moon MA Chari TW Kim AJ Kim P Lee KH Ahn SY Kim 《Bioorganic & medicinal chemistry letters》2012,22(16):5199-5203
A novel synthetic 3,4-dihydropyrimidinone derivative, compound D22 (ethyl 6-methyl-4-(3-phenoxyphenyl)-2-thioxo-3,4-dihydropyrimidine-5-carboxylate), was found to exert anti-inflammatory properties in lipopolysaccharide-stimulated microglial BV-2 cells. Compound D22 reduced the pro-inflammatory factors such as nitric oxide, prostaglandin E(2), tumor necrosis factor-α and interleukin-1β. Moreover, it suppressed the expressions of inducible NO synthase and cyclooxygenase-2. Compound D22 inhibited the activation of mitogen-activated protein kinases. When compound D22-conditioned media from BV-2 cells were applied to N2a cells, neuronal cell death was inhibited via suppression of caspase-3 activation and regulation of Bcl-2 and Bax proteins expression. These results suggest that compound D22 may be useful for treating neurodegenerative diseases related with neuroinflammation. 相似文献
47.
Mishra SK Shrivastav A Maurya RR Patidar SK Haldar S Mishra S 《Protein expression and purification》2012,81(1):5-10
The isolated cyanobacterium containing biopigments like chlorophyll-a, phycoerythrin, phycocyanin, and carotenoid was cultured under different quality of light modes to ascertain biomass and pigment productivity. On the basis of 16S rRNA gene sequence, the isolate was identified as Pseudanabaena sp. Maximum biomass concentration obtained in white-, blue-, and green-light was 0.82, 0.94, and 0.89 g/L, respectively. It was observed that maximum phycoerythrin production was in green light (39.2 mg/L), ensued by blue light (32.2 mg/L), while phycocyanin production was maximum in red light (10.9 mg/L). In yellow light, pigment production as well as the growth rate gradually declined after 12 days. Carotenoid production decreased in blue-, white-, and red-light after 15 days, while in green light it had increased gradually. The present communication suggests that Pseudanabaena sp. can be used for commercial production of phycoerythrin when grown under green light. 相似文献
48.
The proteins LMO4 and DEAF1 contribute to the proliferation of mammary epithelial cells. During breast cancer LMO4 is upregulated, affecting its interaction with other protein partners. This may set cells on a path to tumour formation. LMO4 and DEAF1 interact, but it is unknown how they cooperate to regulate cell proliferation. In this study, we identify a specific LMO4-binding domain in DEAF1. This domain contains an unstructured region that directly contacts LMO4, and a coiled coil that contains the DEAF1 nuclear export signal (NES). The coiled coil region can form tetramers and has the typical properties of a coiled coil domain. Using a simple cell-based assay, we show that LMO4 modulates the activity of the DEAF NES, causing nuclear accumulation of a construct containing the LMO4-interaction region of DEAF1. 相似文献
49.
The ability to synthesize and salvage purines is crucial for colonization by a variety of human bacterial pathogens. Helicobacter pylori colonizes the gastric epithelium of humans, yet its specific purine requirements are poorly understood, and the transport mechanisms underlying purine uptake remain unknown. Using a fully defined synthetic growth medium, we determined that H. pylori 26695 possesses a complete salvage pathway that allows for growth on any biological purine nucleobase or nucleoside with the exception of xanthosine. Doubling times in this medium varied between 7 and 14 hours depending on the purine source, with hypoxanthine, inosine and adenosine representing the purines utilized most efficiently for growth. The ability to grow on adenine or adenosine was studied using enzyme assays, revealing deamination of adenosine but not adenine by H. pylori 26695 cell lysates. Using mutant analysis we show that a strain lacking the gene encoding a NupC homolog (HP1180) was growth-retarded in a defined medium supplemented with certain purines. This strain was attenuated for uptake of radiolabeled adenosine, guanosine, and inosine, showing a role for this transporter in uptake of purine nucleosides. Deletion of the GMP biosynthesis gene guaA had no discernible effect on mouse stomach colonization, in contrast to findings in numerous bacterial pathogens. In this study we define a more comprehensive model for purine acquisition and salvage in H. pylori that includes purine uptake by a NupC homolog and catabolism of adenosine via adenosine deaminase. 相似文献
50.
TK Lai G Biswas S Chatterjee A Dutta C Pal J Banerji N Bhuvanesh JH Reibenspies K Acharya 《Chemistry & biodiversity》2012,9(8):1517-1524
Two new lanostane-type triterpenes, 1 and 2, were isolated from Astraeus hygrometricus. The structures were established by IR, (1) H- and (13) C-NMR, MS, and X-ray crystallographic experiments. The triterpenes exhibited excellent in vitro toxicities against Candida albicans, comparable to standard antifungal antibiotics. The triterpene 2 significantly inhibited the growth of Leishmania donovani promastigotes in vitro. The triterpene skeleton may be considered a template structure in search for new compounds with anticandidal and leishmanicidal activity. 相似文献