全文获取类型
收费全文 | 2317篇 |
免费 | 71篇 |
国内免费 | 21篇 |
出版年
2023年 | 27篇 |
2022年 | 12篇 |
2021年 | 32篇 |
2020年 | 78篇 |
2019年 | 133篇 |
2018年 | 130篇 |
2017年 | 107篇 |
2016年 | 94篇 |
2015年 | 45篇 |
2014年 | 136篇 |
2013年 | 244篇 |
2012年 | 31篇 |
2011年 | 103篇 |
2010年 | 51篇 |
2009年 | 80篇 |
2008年 | 83篇 |
2007年 | 79篇 |
2006年 | 84篇 |
2005年 | 51篇 |
2004年 | 50篇 |
2003年 | 56篇 |
2002年 | 49篇 |
2001年 | 19篇 |
2000年 | 15篇 |
1999年 | 14篇 |
1998年 | 19篇 |
1997年 | 12篇 |
1996年 | 12篇 |
1995年 | 18篇 |
1994年 | 22篇 |
1993年 | 17篇 |
1992年 | 25篇 |
1991年 | 12篇 |
1990年 | 7篇 |
1989年 | 9篇 |
1987年 | 8篇 |
1986年 | 6篇 |
1985年 | 55篇 |
1984年 | 54篇 |
1983年 | 21篇 |
1982年 | 48篇 |
1981年 | 43篇 |
1980年 | 52篇 |
1979年 | 50篇 |
1978年 | 36篇 |
1977年 | 25篇 |
1976年 | 17篇 |
1975年 | 10篇 |
1974年 | 6篇 |
1973年 | 16篇 |
排序方式: 共有2409条查询结果,搜索用时 342 毫秒
1.
Two new pyrrole derivatives Salaciamole (1), Salaciaglycoside A (2), long with one known compound 1H-pyrrole-3-carboxylic acid (3) were isolated from the roots of Salacia amplifolia Merr (Hippocrateaceae). The structures of the new compounds were deduced from their comprehensive spectroscopic analysis including IR, HR-EI-MS, 1H NMR, 13C NMR, DEPT, COSY, HMBC and HMQC. And the structure of the known compound was identified by comparison of their spectral data with those reported in the literature. 相似文献
2.
Four series of para or meta - substituted thiazolylbenzenesulfonamides bearing Cl substituents were designed, synthesized, and evaluated as inhibitors of all 12 catalytically active recombinant human carbonic anhydrase (CA) isoforms. Observed affinities were determined by the fluorescent thermal shift assay and the intrinsic affinities were calculated based on the fractions of binding-ready deprotonated sulfonamide and CA bearing protonated hydroxide bound to the catalytic Zn(II) in the active site. Several compounds exhibited selectivity towards CA IX, an anticancer target. Intrinsic affinities reached 30 pM, while the observed affinities - 70 nM. The structure-intrinsic affinity relationship map of the compounds showed the energetic contributions of the thiazole ring and its substituents. 相似文献
3.
Maria Ida De Michelis Antonella Camelli Franca Rasi-Caldogno 《Plant biology (Stuttgart, Germany)》1993,106(1):20-25
The transport and hydrolytic activities of the plasma membrane (PM) Ca2+ pump were characterized in a PM fraction purified from seedlings of Arabidopsis thaliana by the aqueous two-phase partitioning technique. Ca2+ uptake could be energized by ATP and by ITP (at about 70% the rate sustained by ATP). This characteristic was used to measure the hydrolytic activity of the enzyme as Ca2+-dependent ITPase activity. The PM Ca2+ pump displayed a broad pH optimum around pH 7.2, was drastically inhibited by erythrosin B (EB), and was half-saturated by 60 μM ITP. It was stimulated by CaM, specially at low, non-saturating Ca2+ concentrations. All of these characteristics closely resemble those of the PM Ca2+ pump in other plant materials. Analysis of the effects of EB and other fluorescein derivatives (eosin Y and rose bengal) showed that: i) EB behaved as a competitive inhibitor with respect to ITP; ii) the PM Ca2+ pump was drastically inhibited by concentrations of fluorescein derivatives (submicromolar), much lower than those required to inhibit the PM H+-ATPase; iii) the different fluorescein derivatives were diversely efficient in inhibiting the activities of the Ca2+ pump and of the H+-ATPase of the PM (eosin Y was about 10000-fold, EB 1000-fold and rose bengal only 50-fold more active on the Ca2+ pump than on the H+-ATPase); and iv) the effectiveness of EB in inhibiting the Ca2+ pump was strongly affected by the protein concentration in the assay medium. 相似文献
4.
Jariya Kowapradit Praneet Opanasopit Tanasait Ngawhiranpat Auayporn Apirakaramwong Theerasak Rojanarata Uracha Ruktanonchai Warayuth Sajomsang 《AAPS PharmSciTech》2008,9(4):1143-1152
The aim of this study was to investigate the effect of methylated N-(4-N,N-dimethylaminobenzyl) chitosan, TM-Bz-CS, on the paracellular permeability of Caco-2 cell monolayers and its toxicity towards
the cell lines. The factors affecting epithelial permeability, e.g., degree of quaternization (DQ) and extent of dimethylaminobenzyl
substitution (ES), were evaluated in intestinal cell monolayers of Caco-2 cells using the transepithelial electrical resistance
and permeability of Caco-2 cell monolayers, with fluorescein isothiocyanate dextran 4,400 (FD-4) as a model compound for paracellular
tight-junction transport. Cytotoxicity was evaluated with the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide
viability assay. The results revealed that, at pH 7.4, TM-Bz-CS appeared to increase cell permeability in a concentration-dependent
manner, and this effect was relatively reversible at lower doses of 0.05–0.5 mM. Higher DQ and the ES caused the permeability
of FD-4 to be higher. The cytotoxicity of TM-Bz-CS depended on concentration, %DQ, and %ES. These studies demonstrated that
this novel modified chitosan has potential as an absorption enhancer. 相似文献
5.
In continuation of our study of novel quinolines with anti-inflammatory activity using the Pfitzinger reaction, several new quinoline derivatives were synthesized and tested for their anti-inflammatory and ulcerogenic effect. A docking study on the COX-2 binding pocket was carried out for the target compounds to rationalize the possible selectivity of them against COX-2 enzyme. The most active compounds (5a, 8a and 11a) were found to be superior to celecoxib. Compound 11a demonstrated the highest anti-inflammatory activity as well as the best binding profiles into the COX-2 binding site. Moreover, compounds 9c, 9e, 10a and 11a were devoid of ulcerogenic activity. 相似文献
6.
Three new compounds, 4-{erythro-2-[3-(4-hydroxyl-3-methoxyphenyl)-3-O-β-d-glucopyranosyl-propan-1-ol]}-O-medioresinol (1), (7⿳E,9⿳E,1⿳R*,3⿳S*,5⿳R*,6⿳S*)-5-O-caffeoyl-3-O-dihydrophaseicoylquinic acid (2), and (7⿳E,9⿳E,1⿳R*,3⿳S*,5⿳R*,6⿳S*)-5-O-caffeoyl-4-O-dihydrophaseicoylquinic acid (3), were isolated from Chinese folk herb Erycibe obtusifolia together with six known compounds (49). Their structures were elucidated on the basis of comparisons of literatures and extensive spectroscopic analysis, including UV, IR, HRMS, and 1D and 2D NMR techniques. Further, the cytotoxicities of these compounds were evaluated against five cell lines (HCT-8, Bel-7402, BGC-823, A549, and A2780), but they were inactive against these tumor cell lines (IC50 > 10 μmol/L). 相似文献
7.
Françoise Khuong-Huu Marie-José Magdeleine Jean Santamaria Robert Goutarel 《Phytochemistry》1973,12(7):1813-1816
Malouetine and funtumafrine C have been isolated from the leaves of Malouetia brachyloba, indicating that this species is not very different from M. bequaertiana. Five conanine derivatives have been extracted from the leaves of M. heudelotii, a species which does not contain any alkaloid with a quaternary ammonium function. 相似文献
8.
Magalis Bittner K.Angela Poyser J.Philip Poyser Mario Silva Eduardo Weldt Peter G. Sammes 《Phytochemistry》1973,12(6):1427-1431
Cucurbitacins-D, -F, -H, and the new member 23,24-dihydrocucurbitacin F have been isolated from Crinodendron hookeranium. This is the first report of cucurbitacins in the Elaeocarpaceae. Other components isolated included gallic and ellagic acids, methyl 3-O-methylgallate and an ellagitannin. 相似文献
9.
《Bioorganic & medicinal chemistry letters》2020,30(9):127076
A series of 4-(pyridin-4-yloxy)benzamide derivatives bearing a 5-methylpyridazin-3(2H)-one fragment were designed, synthesized, and evaluated for their biological activity. Most compounds showed effective inhibitory activity against cancer cell lines of A549, HeLa and MCF-7. Among them, the most promising compound 40 showed excellent activity against A549, HeLa and MCF-7 cell lines with IC50 values of 1.03, 1.15 and 2.59 μM, respectively, which was 2.606.95 times more active than that of Golvatinib. The structure-activity relationships (SARs) showed that the introduction of 5-methylpyridazin-3(2H)-one to “5-atom linker” and the modification of the amide with morpholine group were beneficial for enhancing the inhibitory activity of compounds. In addition, the further research on compound 40 mainly include c-Met kinase activity, concentration dependence, apoptosis (acridine orange staining), and molecular docking. 相似文献
10.
《Bioorganic & medicinal chemistry》2014,22(3):1201-1207
Human rhinoviruses (HRVs) are the most common cause of viral respiratory infections and their complications. So far, no anti-viral agent has been approved for prevention or treatment of HRV infections. Pursuing our researches on small molecules with anti-rhinovirus activity, in this paper we describe the synthesis and in vitro anti-HRV 1B and 14 properties of new [2-(2H-chromen-3-yl)vinyl]pyridines and 3-[2-(pyridinyl)vinyl]-4H-chromen-4-ones. Generally, the synthesized compounds interfered with the replication of both serotypes at the micromolar or submicromolar concentrations. Preliminary results on their mechanism of action, performed on selected (E)-2-[2-(2H-chromen-3-yl)vinyl]pyridine, indicate an interference with the early step(s) of HRV 1B and 14 replication, probably at the uncoating level. 相似文献