全文获取类型
收费全文 | 350篇 |
免费 | 21篇 |
出版年
2022年 | 2篇 |
2021年 | 7篇 |
2020年 | 5篇 |
2017年 | 5篇 |
2016年 | 9篇 |
2015年 | 18篇 |
2014年 | 24篇 |
2013年 | 27篇 |
2012年 | 26篇 |
2011年 | 35篇 |
2010年 | 14篇 |
2009年 | 10篇 |
2008年 | 19篇 |
2007年 | 15篇 |
2006年 | 15篇 |
2005年 | 20篇 |
2004年 | 18篇 |
2003年 | 12篇 |
2002年 | 9篇 |
2001年 | 3篇 |
2000年 | 3篇 |
1999年 | 4篇 |
1998年 | 10篇 |
1996年 | 4篇 |
1995年 | 3篇 |
1993年 | 2篇 |
1992年 | 2篇 |
1988年 | 4篇 |
1986年 | 1篇 |
1985年 | 2篇 |
1984年 | 3篇 |
1983年 | 2篇 |
1982年 | 2篇 |
1980年 | 2篇 |
1979年 | 2篇 |
1978年 | 6篇 |
1977年 | 4篇 |
1975年 | 2篇 |
1974年 | 1篇 |
1971年 | 1篇 |
1970年 | 1篇 |
1969年 | 2篇 |
1968年 | 1篇 |
1965年 | 1篇 |
1963年 | 1篇 |
1961年 | 1篇 |
1956年 | 1篇 |
1955年 | 2篇 |
1951年 | 1篇 |
1950年 | 1篇 |
排序方式: 共有371条查询结果,搜索用时 15 毫秒
91.
92.
Sven-Erik Hillver Lena Bjrk Berit Backlund Hk Lourdes Cortizo Gunnar Nordvall Anette M. Johansson Anne Ertan Ingeborg Csregh Lars Johansson Tommy Lewander Uli Hacksell 《Chirality》1996,8(8):531-544
The (S)-enantiomer of 5-fluoro-8-hydroxy-2-(dipropylamino) tetralin [(S)- 2a; (S)-UH301] was the first reported 5-HT1A receptor antagonist. We now give a full account on the synthetic effort leading to the preparation of the racemate and the enantiomers of 2a. The crystal and molecular structure of 2a · HBr has been determined by X-ray diffraction and the absolute configuration has been deduced using statistical tests of the crystallographic R values. The unit cell is tetragonal (P41212) with a = b = 13.2235 (2), c = 39.560(1) Å and contains two crystallographically independent molecules in each asymmetric unit. The two solid state conformers differ in the conformation of the N-propyl groups. The pharmacological characterization of the enantiomers was done by use of in vivo biochemical and behavioural assays in rats. The (R)-enantiomer of 2a is a 5-HT1A receptor agonist of low potency while (S)- 2a does not exhibit any agonist properties at 5-HT1A receptors. As a consequence of the opposing effects of the enantiomers, the racemate, rac- 2a, does not produce any clear-cut effects in rats. The reduced efficacy of (S)- 2a as compared to the well known 5-HT1A receptor agonist 8-hydroxy-2-(dipropylamino)tetralin ( 1; 8-OH-DPAT) may be due to the fluoro-substituent induced negative potential of the aromatic ring. Chirality 8:531–544, 1996. © 1997 Wiley-Liss, Inc. 相似文献
93.
Berit Troost-Kind Martijn J. van Hemert Denise van de Pol Heidi van der Ende-Metselaar Andres Merits Malte Borggrewe Izabela A. Rodenhuis-Zybert Jolanda M. Smit 《PLoS neglected tropical diseases》2021,15(11)
Tomatidine, a natural steroidal alkaloid from unripe green tomatoes has been shown to exhibit many health benefits. We recently provided in vitro evidence that tomatidine reduces the infectivity of Dengue virus (DENV) and Chikungunya virus (CHIKV), two medically important arthropod-borne human infections for which no treatment options are available. We observed a potent antiviral effect with EC50 values of 0.82 μM for DENV-2 and 1.3 μM for CHIKV-LR. In this study, we investigated how tomatidine controls CHIKV infectivity. Using mass spectrometry, we identified that tomatidine induces the expression of p62, CD98, metallothionein and thioredoxin-related transmembrane protein 2 in Huh7 cells. The hits p62 and CD98 were validated, yet subsequent analysis revealed that they are not responsible for the observed antiviral effect. In parallel, we sought to identify at which step of the virus replication cycle tomatidine controls virus infectivity. A strong antiviral effect was seen when in vitro transcribed CHIKV RNA was transfected into Huh7 cells treated with tomatidine, thereby excluding a role for tomatidine during CHIKV cell entry. Subsequent determination of the number of intracellular viral RNA copies and viral protein expression levels during natural infection revealed that tomatidine reduces the RNA copy number and viral protein expression levels in infected cells. Once cells are infected, tomatidine is not able to interfere with active RNA replication yet it can reduce viral protein expression. Collectively, the results delineate that tomatidine controls viral protein expression to exert its antiviral activity. Lastly, sequential passaging of CHIKV in presence of tomatidine did not lead to viral resistance. Collectively, these results further emphasize the potential of tomatidine as an antiviral treatment towards CHIKV infection. 相似文献
94.
95.
Nergard CS Kiyohara H Reynolds JC Thomas-Oates JE Matsumoto T Yamada H Michaelsen TE Diallo D Paulsen BS 《Carbohydrate research》2005,340(11):1789-1801
Structure and immunological characteristics of the pectic arabinogalactan Vk2a (previously reported as Vk100A2a) from the roots of Vernonia kotschyana Sch. Bip. ex Walp. were investigated after enzymatic digestion of the galacturonan moiety and the side chains of the rhamnogalacturonan structure of Vk2a. endo-alpha-D-(1-->4)-Polygalacturonase digestion released the high molecular weight 'hairy region' (Vk2a-HR) and oligogalacturonides. Vk2a-HR consisted of GalA (4-linked) and Rha (2- or 2,4-linked) in a 1:1 ratio, with 60% of Rha branched at C-4. The Rha located in the rhamnogalacturonan core was branched randomly by Gal units. Vk2a-HR was rich in neutral sugars such as Araf 5- (12.2%) and 3,5-substituted (12.8%) and terminally- (14.1%) linked and Gal 4- (13.0%), 3- (0.9%), 6- (2.2%) and 3,6- (1.1%) substituted. Arabinans with chain lengths up to 11 units were identified. Araf residues were attached to C-3 of alpha-L-(1-->5)-Araf chains and to C-4 of Gal residues. Single Gal units and chains of beta-D-(1-->6)-linked galacto di- to penta-saccharides were attached to a beta-D-(1-->3)-galactan core. All the enzyme resistant fractions expressed potent complement fixation and induction of B-cell mitogenic activity, and the present study indicates that there may be several and possibly structurally different active sites involved in the bioactivity of Vk2a. The bioactive sites may be located both in the more peripheral parts of the molecule but also in the inner core of the 'hairy region' or in larger enzyme-resistant chains. 相似文献
96.
Hansen B Longati P Elvevold K Nedredal GI Schledzewski K Olsen R Falkowski M Kzhyshkowska J Carlsson F Johansson S Smedsrød B Goerdt S Johansson S McCourt P 《Experimental cell research》2005,303(1):160-173
Liver sinusoidal endothelial cells (LSECs) mediate clearance of hyaluronan (HA) and scavenger receptor ligands, for example, advanced glycation end product (AGE)-modified proteins and oxidized lipids from the circulation. We recently cloned stabilin-1 and -2, two members of a novel family of transmembrane proteins expressed in LSECs. By using primary LSECs and HEK293 cells separately expressing either stabilin, we have investigated their roles in the early events of endocytosis with respect to localization, ligand-binding properties, and associations with clathrin and adaptor protein (AP)-2. Both stabilins were present at the cell surface, although surface levels of stabilin-1 were limited. In addition, stabilins were present in early endosomal antigen (EEA)-1+ organelles colocalizing with endocytosed AGE-modified bovine serum albumin (BSA). Treating cells with monensin further pronounced this distribution. Recombinant stabilin-2, but not recombinant stabilin-1, bound HA and the scavenger receptor ligands AGE-modified BSA, formaldehyde-treated BSA, and collagen N-terminal propeptides. In LSECs, both stabilins were associated with clathrin and AP-2, but not with each other. These interactions did not change upon addition of exogenous HA, suggesting that stabilins are constitutively internalized. In conclusion, hepatic stabilins are both present in the early endocytic pathway, associating with clathrin/AP-2, but whereas stabilin-2 has a clear scavenging profile, stabilin-1 does not recognize these ligands. 相似文献
97.
Sondén B Kocíncová D Deshayes C Euphrasie D Rhayat L Laval F Frehel C Daffé M Etienne G Reyrat JM 《Molecular microbiology》2005,58(2):426-440
The cell envelope of mycobacteria is a complex multilaminar structure that protects the cell from stresses encountered in the environment, and plays an important role against the bactericidal activity of immune system cells. The outermost layer of the mycobacterial envelope typically contains species-specific glycolipids. Depending on the mycobacterial species, the major glycolipid localized at the surface can be either a phenolglycolipid or a peptidoglycolipid (GPL). Currently, the mechanism of how these glycolipids are addressed to the cell surface is not understood. In this study, by using a transposon library of Mycobacterium smegmatis and a simple dye assay, six genes involved in GPLs synthesis have been characterized. All of these genes are clustered in a single genomic region of approximately 60 kb. We show by biochemical analyses that two non-ribosomal peptide synthetases, a polyketide synthase, a methyltransferase and a member of the MmpL family are required for the biosynthesis of the GPLs backbone. Furthermore, we demonstrate that a small integral membrane protein of 272 amino acids named Gap (gap: GPL addressing protein) is specifically required for the transport of the GPLs to the cell surface. This protein is predicted to contain six transmembrane segments and possesses homologues across the mycobacterial genus, thus delineating a new protein family. This Gap family represents a new paradigm for the transport of small molecules across the mycobacterial envelope, a critical determinant of mycobacterial virulence. 相似文献
98.
Jensen BP Smith CJ Bailey C Rodgers C Wilson ID Nicholson JK 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》2004,809(2):279-285
ICP-MS, HPLC-ICP-MS and HPLC-ICP-MS/ESI-MS have been applied to determine the disposition and metabolic fate of 2-, 3- and 4-iodobenzoic acids following intraperitoneal administration at 50 mg kg(-1) to male bile duct cannulated rats. Quantitative excretion balance studies based on the determination of the total iodine content of urine and bile showed that all three iodobenzoic acids were rapidly excreted. Recoveries ranging from 95 to 105% of the administered doses were achieved within 24 h of administration. Metabolite profiles for urine and bile showed extensive metabolism with unchanged iodobenzoic acids forming a minor part of the total. A combination of alkaline hydrolysis and MS enabled the identification of the major metabolites of all three iodobenzoic acids as glycine and ester glucuronide conjugates with very little if any of the parent compounds excreted unchanged. 相似文献
99.
100.