全文获取类型
收费全文 | 1082篇 |
免费 | 53篇 |
国内免费 | 2篇 |
专业分类
1137篇 |
出版年
2022年 | 9篇 |
2021年 | 22篇 |
2020年 | 18篇 |
2019年 | 16篇 |
2018年 | 33篇 |
2017年 | 27篇 |
2016年 | 43篇 |
2015年 | 56篇 |
2014年 | 65篇 |
2013年 | 70篇 |
2012年 | 84篇 |
2011年 | 111篇 |
2010年 | 49篇 |
2009年 | 42篇 |
2008年 | 73篇 |
2007年 | 78篇 |
2006年 | 95篇 |
2005年 | 43篇 |
2004年 | 64篇 |
2003年 | 57篇 |
2002年 | 37篇 |
2001年 | 4篇 |
2000年 | 3篇 |
1999年 | 8篇 |
1998年 | 7篇 |
1997年 | 6篇 |
1996年 | 4篇 |
1995年 | 5篇 |
1994年 | 2篇 |
1990年 | 1篇 |
1988年 | 2篇 |
1987年 | 1篇 |
1982年 | 1篇 |
1972年 | 1篇 |
排序方式: 共有1137条查询结果,搜索用时 15 毫秒
991.
992.
Anna Stankiewicz Katarzyna Kaczorowska Ryszard Bugno Aneta Kozio Maria H. Paluchowska Grzegorz Burnat Barbara Chrucicka Paulina Chorobik Piotr Braski Joanna M. Wieroska Beata Duszyska Andrzej Pilc Andrzej J. Bojarski 《Journal of enzyme inhibition and medicinal chemistry》2022,37(1):211
Considering the allosteric regulation of mGlu receptors for potential therapeutic applications, we developed a group of 1,2,4-oxadiazole derivatives that displayed mGlu4 receptor positive allosteric modulatory activity (EC50 = 282–656 nM). Selectivity screening revealed that they were devoid of activity at mGlu1, mGlu2 and mGlu5 receptors, but modulated mGlu7 and mGlu8 receptors, thus were classified as group III-preferring mGlu receptor agents. None of the compounds was active towards hERG channels or in the mini-AMES test. The most potent in vitro mGlu4 PAM derivative 52 (N-(3-chloro-4-(5-(2-chlorophenyl)-1,2,4-oxadiazol-3-yl)phenyl)picolinamide) was readily absorbed after i.p. administration (male Albino Swiss mice) and reached a maximum brain concentration of 949.76 ng/mL. Five modulators (34, 37, 52, 60 and 62) demonstrated significant anxiolytic- and antipsychotic-like properties in the SIH and DOI-induced head twitch test, respectively. Promising data were obtained, especially for N-(4-(5-(2-chlorophenyl)-1,2,4-oxadiazol-3-yl)-3-methylphenyl)picolinamide (62), whose effects in the DOI-induced head twitch test were comparable to those of clozapine and better than those reported for the selective mGlu4 PAM . ADX88178相似文献
993.
Mateusz Kciuk Adrianna Gieleciska Somdutt Mujwar Mariusz Mojzych Beata Marciniak Rafa Drozda Renata Kontek 《Journal of enzyme inhibition and medicinal chemistry》2022,37(1):1278
Carbonic anhydrases IX and CAXII (CAIX/CAXII) are transmembrane zinc metalloproteins that catalyze a very basic but crucial physiological reaction: the conversion of carbon dioxide into bicarbonate with a release of the proton. CA, especially CAIX and CAXII isoforms gained the attention of many researchers interested in anticancer drug design due to pivotal functions of enzymes in the cancer cell metastasis and response to hypoxia, and their expression restricted to malignant cells. This offers an opportunity to develop new targeted therapies with fewer side effects. Continuous efforts led to the discovery of a series of diverse compounds with the most abundant sulphonamide derivatives. Here we review current knowledge considering small molecule and antibody-based targeting of CAIX/CAXII in cancer. 相似文献
994.
Mutagenic pollution of environment is a global and important problem. This includes marine environment. Although many mutagenicity assays have been developed, there are specific problems with testing marine water and sediments for mutagenic contamination. One of them is the fact that most of genetically modified strains used in commonly available microbiological mutagenicity assays, like Escherichia coli or Salmonella, survive relatively poorly in marine waters, especially those of higher salinity. Thus, alternative assays have been developed, in which bacteria occurring naturally in marine habitats are employed. These assays, reviewed in this article, appear to be useful in testing not only marine samples but also can be used in other approaches, which involve detection and estimation of the amount of mutagenic compounds. 相似文献
995.
Beata Cwalina Ludmiła Węglarz Zofia Dzierzewicz Tadeusz Wilczok 《Applied microbiology and biotechnology》1988,28(1):100-102
Summary The leaching activity of five batches of Thiobacillus ferrooxidans, strain F26-77, cultivated under various conditions, towards elemental sulphur, ferrous ions, pyrite, covellite, chalcopyrite and sphalerite was studied. The activities of sulphite oxidase, thiosulphate oxidase and rhodanese were determined in crude, cell-free bacterial extracts. The effectiveness of leaching was directly correlated with the enzymic activity of the cultures. The results suggest that the activities of the enzymes metabolizing sulphur and its inorganic compounds in Thiobacillus ferrooxidans, or bacterial leaching activity on sulphur and sulphides, rather than the rate of oxidation of ferrous ions, should be taken as the criterion of usefulness for the leaching of sulphide minerals. 相似文献
996.
The TYLCV-tolerant tomato line MP-1 is characterized by superior transformation competence 总被引:3,自引:0,他引:3
Barg Rivka; Pilowsky Meir; Shabtai Sara; Carmi Nir; Szechtman Alejandro D.; Dedicova Beata; Salts Yehiam 《Journal of experimental botany》1997,48(11):1919-1923
The tomato line MP-1 excels the cultivars commonly used fortransformation with regard to the speed of regeneration, percentageof transformation and frequency of phenotypically normal transgenicplants. These characteristics, together with its tolerance toTomato Yellow Leaf Curl Virus, make line MP-1 very suitablefor large scale generation of transgenic tomatoes. Key words: Lycopersicon esculentum, transformatioefficient tomato line 相似文献
997.
Genowefa Misztal Beata Paw Janusz S. Skierski Ewa Jagie
o-Wjtowicz 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》1999,731(2):341
A new, simple and accurate high-performance liquid chromatography (HPLC) method for the determination of formycin A in plasma is presented. The samples were chromatographed on a LiChrosorb RP-18 column after purification using a Bakerbond SPE column. The mobile phase was methanol–0.067 M phosphate buffer, pH 4.20 (1:4, v/v) containing 0.005 M sodium hexanesulfonate. Azathioprine was applied as an internal standard. UV detection was carried out at 293 nm. The method was tested for linearity (over the range 0.1–9.0 μg/ml). The recovery was 91.89% (mean). The described method has been successfully applied to the quantitative determination of formycin A in plasma and should be useful for clinical and bioavailability investigations. 相似文献
998.
Wojciech Kamysz Beata Mickiewicz Katarzyna Greber Sylwia Rodziewicz‐MotowidŁo 《Journal of peptide science》2007,13(5):327-333
Temporin A (TA) is a small, basic and highly hydrophobic peptide, isolated from the skin of the European red frog, Rana temporaria. The TA (FLPLIGRVLSGIL-NH2) displays a broad spectrum of anti-microbial activity against Gram-positive bacteria and fungi Candida albicans. In this study we investigate the solution structure of two TA retro-analogues, (6-1)(7-13)-TA (GILPLFRVLSGIL-NH2) and retro-TA (LIGSLVRGILPLF-NH2) by using nuclear magnetic resonance (NMR). The 3D solution structure of the analogues was established by using inter-proton distances and vicinal coupling constants in the Simulated Annealing (SA) calculations (XPLOR program). The NMR conformational studies show the existence of the helical structure in the middle part of the (6-1)(7-13)-TA peptide and an unordered structure of the retro-TA analogue under the D3-TFE/H2O (3:7, v/v) conditions. Our investigations have shown that the hydrophobic cluster at N-terminus with the Pro amino acid residue in position 3 or 4, the helical structure and the amphipathic character of the peptide are responsible for the anti-microbial activity of the TA analogues. 相似文献
999.
Stefan Irmler Heike Schäfer Beata Beisert Doris Rauhut & Hélène Berthoud 《FEMS microbiology letters》2009,295(1):67-76
The trans -sulfuration pathways allow the interconversion of cysteine and methionine with the intermediary formation of cystathionine and homocysteine. The genome database of Lactobacillus casei ATCC 334 provides evidence that this species cannot synthesize cysteine from methionine via the trans -sulfuration pathway. However, several L. casei strains use methionine as the sole sulfur source, which implies that these strains can convert methionine to cysteine. Cystathionine synthases and lyases play a crucial role in the trans -sulfuration pathway. By applying proteomic techniques, we have identified a protein in cell-free extracts of L. casei , which showed high homology to a gene product encoded in the genome of Lactobacillus delbrueckii ssp. bulgaricus, Streptococcus thermophilus and Lactobacillus helveticus but not in the genome of L. casei ATCC 334. The presence of the gene was only found in strains able to grow on methionine as the sole sulfur source. Moreover, two gene variants were identified. Both gene variants were cloned and expressed heterologously in Escherichia coli . The recombinant enzymes exhibited cystathionine lyase activity in vitro and also cleaved cysteine, homocysteine and methionine releasing volatile sulfur compounds. 相似文献
1000.
Ghosh Roy S Sadigh B Datan E Lockshin RA Zakeri Z 《World journal of biological chemistry》2014,5(2):93-105
Flaviviruses, ss(+) RNA viruses, include many of mankind's most important pathogens. Their pathogenicity derives from their ability to infect many types of cells including neurons, to replicate, and eventually to kill the cells. Flaviviruses can activate tumor necrosis factor α and both intrinsic(Bax-mediated) and extrinsic pathways to apoptosis. Thus they can use many approaches for activating these pathways. Infection can lead to necrosis if viral load is extremely high or to other types of cell death if routes to apoptosis are blocked. Dengue and Japanese Encephalitis Virus can also activate autophagy. In this case the autophagy temporarily spares the infected cell, allowing a longer period of reproduction for the virus, and the autophagy further protects the cell against other stresses such as those caused by reactive oxygen species. Several of the viral proteins have been shown to induce apoptosis or autophagy on their own, independent of the presence of other viral proteins. Given the versatility of these viruses to adapt to and manipulate the metabolism, and thus to control the survival of, the infected cells, we need to understand much better how the specific viral proteins affect the pathways to apoptosis and autophagy. Only in this manner will we be able to minimize the pathology that they cause. 相似文献