全文获取类型
收费全文 | 4044篇 |
免费 | 373篇 |
国内免费 | 1090篇 |
专业分类
5507篇 |
出版年
2024年 | 52篇 |
2023年 | 158篇 |
2022年 | 199篇 |
2021年 | 236篇 |
2020年 | 218篇 |
2019年 | 295篇 |
2018年 | 196篇 |
2017年 | 166篇 |
2016年 | 163篇 |
2015年 | 211篇 |
2014年 | 219篇 |
2013年 | 295篇 |
2012年 | 165篇 |
2011年 | 217篇 |
2010年 | 203篇 |
2009年 | 196篇 |
2008年 | 225篇 |
2007年 | 201篇 |
2006年 | 218篇 |
2005年 | 234篇 |
2004年 | 168篇 |
2003年 | 185篇 |
2002年 | 159篇 |
2001年 | 101篇 |
2000年 | 79篇 |
1999年 | 81篇 |
1998年 | 91篇 |
1997年 | 59篇 |
1996年 | 66篇 |
1995年 | 53篇 |
1994年 | 39篇 |
1993年 | 44篇 |
1992年 | 37篇 |
1991年 | 26篇 |
1990年 | 28篇 |
1989年 | 21篇 |
1988年 | 21篇 |
1987年 | 17篇 |
1986年 | 17篇 |
1985年 | 15篇 |
1984年 | 25篇 |
1983年 | 16篇 |
1982年 | 21篇 |
1981年 | 18篇 |
1980年 | 12篇 |
1979年 | 12篇 |
1977年 | 7篇 |
1976年 | 5篇 |
1975年 | 4篇 |
1973年 | 5篇 |
排序方式: 共有5507条查询结果,搜索用时 15 毫秒
41.
Mytichitin-CB was isolated from Mytilus coruscus in 2014. This antimicrobial peptide shows a weak inhibitory effect on Gram-negative bacteria but inhibits the growth of Gram-positive bacteria and fungi efficiently. Here, a C-terminal hemagglutinin and 6×Histidine (HA-6×His) double tagged three tandem repeats of Mytichitin-CB (3×Mytichitin-CB) with a molecular weight of about 21.5 kDa was expressed in Chlamydomonas reinhardtii. The recombinant 3×Mytichitin-CB was stably expressed following continuous sixth passages of cells and inhibited the growth of both Gram-negative and Gram-positive bacteria at maximum inhibitory concentration (MIC) values between 30 and 50 μg/mL. 3×Mytichitin-CB was stable in terms of its antibacterial activity when treated by a wide range of temperatures and pHs and was resistant to digestion by various proteases. C. reinhardtii-derived 3×Mytichitin-CB had low hemolytic activity and cell cytotoxicity. Moreover, 3×Mytichitin-CB efficiently caused changes on the cell morphology by destroying membrane integrity of the tested bacteria. Our data thus, for the first time, show that C. reinhardtii is a suitable host for stably expressing recombinant 3×Mytichitin-CB, which possesses potent antibacterial properties. 相似文献
42.
阴道微生态是由阴道的局部解剖结构、周期性的内分泌变化、阴道局部免疫系统和阴道内微生物菌群共同组成的阴道环境和生态系统。多项研究证实阴道微生态失调通过局部炎症因子释放、黏膜免疫应答的改变和局部代谢变化,可引起早产的发生。阴道内小分子物质如糖类、短链脂肪酸和胺类通过代谢路径和代谢产物在阴道微生态失调与早产的发病机制起作用。近年来,阴道微生态的理念得到重视,治疗方法由传统的抗生素治疗转向了综合治疗,目的是恢复正常阴道菌群和阴道上皮黏膜免疫系统。但阴道微生态与宿主之间存在复杂的相互作用,因此仍需要进一步的研究。 相似文献
43.
Kimia Ekramzadeh Chantal Brämer Thore Frister Jörg Fohrer Andreas Kirschning Thomas Scheper Sascha Beutel 《Biotechnology progress》2020,36(2):e2935
The patchoulol synthase (PTS) from Pogostemon cablin is a versatile sesquiterpene synthase and produces more than 20 valuable sesquiterpenes by conversion of the natural substrate farnesyl pyrophosphate (FPP). PTS has the potential to be used as a biocatalyst for the production of valuable sesquiterpenes such as (−)-patchoulol. The objective of the present study is to develop an efficient biotransformation and to characterize the biocatalytic mechanism of the PTS in detail. For this purpose, soluble PTS was prepared using an optimized cultivation protocol and continuous downstream process with a purity of 98%. The PTS biotransformation was then optimized regarding buffer composition, pH-value, and temperature for biotransformation as well as functional and kinetic properties to improve productivity. For the bioconversion of FPP, the highest enzyme activity was reached with the 2-(N-morphlino)ethanesulfonic acid (MES) buffer containing 10% (v/v) glycerol and 10 mM MgCl2 at pH 6.4 and 34°C. The PTS showed an unusual substrate inhibition for sesquiterpene synthases indicating an intermediate sesquiterpene formed in the active center. Deuteration experiments were used to gain further insights into the biocatalytic mechanism described in literature. Thus it could be shown that a second substrate binding site must be responsible for substrate inhibition and that further protonation and deprotonation steps are involved in the reaction mechanism. 相似文献
44.
Golgi α-mannosidase II (GMII) is a Family 38 glycosyl hydrolase involved in the eukaryotic N-glycosylation pathway in protein synthesis. Understanding of its catalytic mechanism has been of interest for the development of specific inhibitors that could lead to novel anti-metastatic or anti-inflammatory compounds. The active site of GMII has been characterized by structural studies of the Drosophila homologue (dGMII) and unusually contains a Zn atom which forms contacts with substrate analogues, stabilized catalytic intermediates, and other inhibitors observed in the active site. In this contribution, we analyze the structure of the sugar mimetic compound noeuromycin complexed with dGMII. Distortions of the conformation of this inhibitor, together with similar observations from other complexes, have permitted us to propose specific roles for the Zn atom in the chemical mechanism of catalysis of Family 38 glycosidase. Such insights have relevance to efforts to formulate novel, specific inhibitors of GMII. 相似文献
45.
《Journal of receptor and signal transduction research》2013,33(3):221-232
AbstractMembers of the sortase enzyme super family decorate the surfaces of Bacillus anthracis cell wall with proteins that play key roles in microbial pathogenesis and its biofilm formation. Bacillus anthracis Sortase-A (Ba-SrtA) is a potential target for new therapeutics as it is required for B. anthracis survival and replication within macrophages. An understanding of the binding site pocket and substrate recognition mechanism by SrtA enzymes may serve to be beneficial in the rational development of sortase inhibitors. Here, the LPXTG signal peptide-based competitive inhibitors are screened against the Ba-SrtA and compounds with reasonable inhibition, specificity, and mechanisms of inactivation of SrtA have been covered. The screened compounds are experimentally validated against the phylogenetically similar Gram-positive pathogen B. cereus. In situ microscopic visualizations suggest that these screened compounds showed the microbial and biofilm inhibitory activity against B. cereus. It facilitates the further development of these molecules into useful anti-infective agents to treat infections caused by B. anthracis and other Gram-positive pathogens. These results provide insight into basic design principles for generating new clinically relevant lead molecules. It also provides an alternative strategy where a screened ligand molecule can be used in combination to battle increasingly against the Gram-positive pathogens. 相似文献
46.
《Journal of enzyme inhibition and medicinal chemistry》2013,28(3):189-193
AbstractInitial rate kinetic studies of lactate dehydrogenase with ketomalonate and NADH as substrates suggest that this enzymatic system is adapted to a rapid equilibrium ordered bi-bi ternary complex mechanism. The application of the reaction product inhibition method reveals the existence of the enzyme-NADH-hydroxy-malonate and enzyme-NAD+-ketomalonate abortive complexes. This kinetic behaviour is confirmed by the differential inhibition induced by several alternate products on the pyruvate-lactate dehydrogenase-NADH and ketomalonate-lactate dehydrogenase-NADH systems. 相似文献
47.
Among the plant life-forms, lianas, the wood climbers still remain less studied than trees. The forests of Eastern Ghats of India are also relatively under studied compared with the Western Ghats biodiversity hotspot. We conducted a large-scale, landscape-level investigation of liana diversity in six hill complexes of the South Eastern Ghats, which covers 4297 km2. We divided the study area into 6.25 km × 6.25 km grids and within each grid a 0.5 ha (5 m × 1000 m) transect was established and all lianas ≥1.5 cm diameter at breast height (dbh) were inventoried in 110 transects totalling a 55-ha area. Liana diversity totalled 143 species in 83 genera and 37 families in the 55 ha sampled. Of these 20 species (28.6%) were endemic to peninsular India and 7 (10%) species belonged to the rare and endangered category. Liana species richness ranged from 8–35 species and density 95–544 individuals per transect. A total of 32 033 liana individuals were enumerated in the 55 ha and the mean abundance was 291 individuals per transect. Across sites, liana abundance varied significantly, but not species richness and basal area. Asclepiadaceae (13 species, 9%) and Apocynaceae (11 species, 8%) constituted the most diverse liana families, followed by Papilionaceae, Vitaceae (10 each, 7%), Convolvulaceae, Mimosaceae, Oleaceae (8 each, 6%), Capparaceae, Rhamnaceae (7 each, 5%) and Menispermaceae (5 species, 3%). In liana stem size distribution, the lowest diameter class (1.5–3 cm dbh) accounted for greatest species richness (137 species, 96%), abundance (27 358 individuals, 85%) and basal area (13.5 m2, 36%). The stem twiners were the predominant climber type in terms of species richness (61 species, 42.65%), whereas the armed scramblers were abundant due to stem density (21 571 individuals, 67.34%). The dispersal modes of lianas, assessed by fruit types, revealed zoochory as the prevalent mode (85 species, 59%) indicating the faunal dependence of lianas in the Eastern Ghats landscape. Liana diversity of the Eastern Ghats was compared with inventories made across the tropics. With these baseline data generated on lianas, the importance of biodiversity conservation of the already fragmented South Eastern Ghats region is underlined and potential areas of further research on liana ecology are suggested. 相似文献
48.
Sibel Suzen Pinar Bozkaya Tulay Coban Doğu Nebioğlu 《Journal of enzyme inhibition and medicinal chemistry》2013,28(4):405-411
Oxidative stress has been implicated in the development of many neurodegenerative diseases and also responsible from aging and some cancer types. Indolic compounds are a broad family of substances present in microorganisms, plants and animals. They are mainly related to tryptophan metabolism, and present particular properties that depend on their respective chemical structures. Due to free radical scavenger and antioxidant properties of indolic derivatives such as indolinic nitroxides and melatonin, a series of 2-phenyl indole derivatives were prepared and their in vitro effects on rat liver lipid peroxidation levels, superoxide formation and DPPH stable radical scavenging activities were determined against melatonin, BHT and α-tocopherol. The compounds significantly inhibited (72–98%) lipid peroxidation at 10? 3 M. These values were similar to that observed with BHT (88%). Possible structure–activity relationships of the compounds were discussed. 相似文献
49.
《Journal of enzyme inhibition and medicinal chemistry》2013,28(3):421-429
A theoretical study on the binding conformations and the quantitative structure–activity relationship (QSAR) of combretastatin A4 (CA-4) analogs as inhibitors toward tubulin has been carried out using docking analysis and comparative molecular field analysis (CoMFA). The appropriate binding orientations and conformations of these compounds interacting with tubulin were revealed by the docking study; and a 3D-QSAR model showing significant statistical quality and satisfactory predictive ability was established, in which the correlation coefficient (R2) and cross-validation coefficient (q2) were 0.955 and 0.66, respectively. The same model was further applied to predict the pIC50 values for 16 congeneric compounds as external test set, and the predictive correlation coefficient R2pred reached 0.883. Other tests on additional validations further confirmed the satisfactory predictive power of the model. In this work, it was very interesting to find that the 3D topology structure of the active site of tubulin from the docking analysis was in good agreement with the 3D-QSAR model from CoMFA for this series of compounds. Some key structural factors of the compounds responsible for cytotoxicity were reasonably presented. These theoretical results can offer useful references for understanding the action mechanism and directing the molecular design of this kind of inhibitor with improved activity. 相似文献
50.
A novel chemiluminescence (CL) method was developed for the determination of cefazolin sodium based on the CL reaction between the [Cu(HIO6)2]5‐Cu(III) complex and luminol in alkaline solution. Results showed that CL emission of Cu(III) complex–luminol in alkaline medium was significantly different from that in acidic medium. A possible mechanism of the enhanced effect of cefazolin on CL emission of the [Cu(HIO6)2]5‐‐ luminol system was proposed. The effect of the reaction conditions on CL emissions was examined. Under optimized conditions, a good linear relationship was obtained between CL intensity and concentrations of cefazolin sodium in the range of 2.0 x 10‐8 to 2.0 x 10‐6 g/mL with a correlation coefficient of R2 = 0.9978. The limit of detection was 4.58 x 10‐9 g/mL. The proposed method was applied for the determination of cefazolin sodium in real samples with recoveries of 82.0‐109% with an RSD of 0.7‐2.1%. The proposed method was successfully used for the determination of cefazolin sodium in injectable powder preparations and human urine with satisfactory results. Copyright © 2012 John Wiley & Sons, Ltd. 相似文献