全文获取类型
收费全文 | 742篇 |
免费 | 48篇 |
专业分类
790篇 |
出版年
2022年 | 4篇 |
2021年 | 7篇 |
2018年 | 9篇 |
2017年 | 7篇 |
2016年 | 10篇 |
2015年 | 15篇 |
2014年 | 23篇 |
2013年 | 25篇 |
2012年 | 43篇 |
2011年 | 56篇 |
2010年 | 33篇 |
2009年 | 28篇 |
2008年 | 31篇 |
2007年 | 37篇 |
2006年 | 34篇 |
2005年 | 35篇 |
2004年 | 34篇 |
2003年 | 31篇 |
2002年 | 34篇 |
2001年 | 11篇 |
2000年 | 12篇 |
1999年 | 13篇 |
1998年 | 17篇 |
1997年 | 15篇 |
1996年 | 14篇 |
1995年 | 6篇 |
1994年 | 9篇 |
1993年 | 13篇 |
1992年 | 6篇 |
1991年 | 11篇 |
1990年 | 8篇 |
1989年 | 9篇 |
1988年 | 7篇 |
1987年 | 6篇 |
1986年 | 11篇 |
1985年 | 7篇 |
1984年 | 7篇 |
1983年 | 8篇 |
1982年 | 14篇 |
1981年 | 9篇 |
1980年 | 8篇 |
1979年 | 9篇 |
1978年 | 11篇 |
1977年 | 8篇 |
1976年 | 3篇 |
1975年 | 4篇 |
1974年 | 4篇 |
1972年 | 5篇 |
1967年 | 3篇 |
1965年 | 4篇 |
排序方式: 共有790条查询结果,搜索用时 0 毫秒
61.
Comparative modeling of the latent form of a plant catechol oxidase using a molluskan hemocyanin structure 总被引:2,自引:0,他引:2
The structure of the precursor form of catechol oxidase from sweet potatoes (Ipomoea batatas) has been modeled on the basis of the 3D structural data of mature catechol oxidase [Nat. Struct. Biol. 5 (1998) 1084] and of hemocyanin from giant octopus (Octopus dofleini) [J. Mol. Biol. 278 (1998) 855]. A C-terminal extension peptide is found in the cDNA sequence but not in the purified, mature form of catechol oxidase. Superimposition of the 3D structures of the native hemocyanin and catechol oxidase reveals a close relationship except for an additional C-terminal domain only found in the hemocyanin structure. As sequence alignment shows good homology this domain of the hemocyanin structure was used as a template to model the 3D structure of the C-terminal extension peptide of catechol oxidase. As hemocyanins show no or only weak catecholase activity due to this domain this indicates an inhibitory function of this extension peptide. Beside this possible shielding function for the precursor form, evidence for a function in copper-uptake also increases due to the location of three histidine residues in the model. 相似文献
62.
Dietrich G Mollenkopf HJ Weber H Knapp B Diehl KD Hess J Blackkolb F Bröker M Kaufmann SH Hundt E 《Journal of biotechnology》2002,96(3):259-270
The Mycobacterium bovis BCG vaccine for commercial use is classically produced as surface pellicles by culture on synthetic medium. Under these conditions, reproducibility of the cultures and quality assessment are hampered by slow growth of the bacilli, the formation of bacterial aggregates and a high proportion of dead bacilli after processing and final formulation of the vaccine. Here, we established dispersed cultures of M. bovis BCG in synthetic media in small-scale bioreactors. These cultures allow recording and adjusting of culture parameters and give rise to single bacilli with a high degree of live bacteria. In the murine model, bioreactor-grown M. bovis BCG exhibited slightly stronger replication and persistence than the vaccine produced under the classical conditions. The protective efficacy against challenge with M. tuberculosis was identical for both vaccine preparations. 相似文献
63.
A novel type of uracil-DNA glycosylase mediating repair of hydrolytic DNA damage in the extremely thermophilic eubacterium Thermus thermophilus 下载免费PDF全文
Spontaneous hydrolytic deamination of DNA cytosine and 5-methyl-cytosine residues is an abundant source of C/G (5-meC/G) to T/A transition mutations. As a result of this pressure, at least six different families of enzymes have evolved that initiate repair at U/G (T/G) mispairs, the relevant pre-mutagenic intermediates. The necessarily higher rate of the process at elevated temperatures must pose a correspondingly accentuated problem to contemporary thermophilic organisms and may have been a serious bottleneck in early evolution when life passed through a phase of very high ambient temperatures. Here we show that Thermus thermophilus, an aerobic, Gram-negative eubacterium thriving at up to 85°C, harbors two uracil-DNA glycosylases (UDGs), termed TTUDGA and TTUDGB. According to both amino acid sequence and enzymatic properties, TTUDGA clearly belongs to the family of ‘thermostable UDGs’. TTUDGB shares with TTUDGA 23% sequence identity, but differs from it in profound functional aspects. TTUDGB, unlike TTUDGA, does not act upon uracil residues in the context of single-stranded DNA whereas both enzymes process various double-stranded substrates, albeit with different preferences. TTUDGB shows a number of sequence features characteristic of the UDG superfamily, but surprisingly lacks any polar residue within its so-called motif 1 (GLAPG-X10-F). This finding is in conflict with a previously assumed crucial catalytic role of motif 1 in water activation and supports a more recently suggested alternative of a dissociative (‘SN1-type’) reaction mechanism. Together, the characteristics of TTUDGB and its homologs in other organisms define a novel family of UDG repair enzymes. 相似文献
64.
Paschke R Kalbitz J Paetz C Luckner M Mueller T Schmoll HJ Mueller H Sorkau E Sinn E 《Journal of inorganic biochemistry》2003,94(4):335-342
This report continues our work on new compounds which consist of three functional parts--a transport fragment, a spacer and a biologically active 'drug' component. Here cholic acid functions as the transport fragment, linked via an alkyl spacer to a carboplatin analog, representing the drug (carbo-ChAPt-Fig. 1). We describe the synthesis and characterization of the series of complexes [Pt(Cyclobutane-1,1-dicarboxylato)(diamine)], [diamine=CholCOO(CH(2))(n)CH(CH(2)NH(2))(2) and THP(CH(2))(n)CH-(CH(2)NH(2))(2), n=4, 6, 8, 11]. The compounds were characterized by elemental analysis and NMR-measurements. Cytostatic activity data are given. In general, the cytostatic activity is similar to that of the parent compound and is strongly influenced by the length of the alkyl chain spacer separating the drug and transport fragments, the ones with long chain spacers being more toxic than the parent complexes. Preliminary investigations indicate the ability of the ChAPt to break resistance of tumor cells against common platinum tumor drugs, e.g. cisplatin. They are effective even on cell lines that have developed resistance to other drugs such as cis- and carboplatin. They are more cytotoxic so they are potentially effective at lower dose concentrations. The mode of cell death was examined by trypan-blue exclusion test and DNA gelelectrophoresis. Typical fragmentation of DNA was observed and the cells were still able to exclude trypan-blue. 相似文献
65.
Timoshenko AV Gorudko IV Maslakova OV André S Kuwabara I Liu FT Kaltner H Gabius HJ 《Molecular and cellular biochemistry》2003,250(1-2):139-149
Cell surface glycans present docking sites to endogenous lectins. With growing insight into the diversity of lectin families it becomes important to answer the question on the activity profiles of individual family members. Focusing on galectins (-galactoside-binding proteins without Ca2+-requirement sharing the jelly-roll-like folding pattern), this study was performed to assess the potency of proto-type galectins (galectins-1 and -7 and CG-16) and the chimera-type galectin-3 to elicit selected cell responses by carbohydrate-dependent surface binding and compare the results. The galectins, except for galectin-1, were found to enhance detergent (SDS)-induced hemolysis of human erythrocytes to different degrees. Their ability to confer increased membrane osmofragility thus differs. Aggregation of neutrophils, thymocytes and platelets was induced by the proto-type galectin-1 but not -7, by CG-16 and also galectin-3. Cell-type-specific quantitative differences and the importance of the fine-specificity of the galectin were clearly apparent. In order to detect cellular responses based on galectin binding and bridging of cells the formation of haptenic-sugar-resistant (HSR) intercellular contacts (an indicator of post-binding signaling) was monitored. It was elicited by CG-16 and galectin-1 but not galectin-3, revealing another level at which activities of individual galectins can differ. Acting as potent elicitor of neutrophil aggregation, CG-16-dependent post-binding effects were further analyzed. Carbohydrate-dependent binding to the neutrophils' surface led to a sustained increase of cytoplasmic Ca2+ concentration in a dose-dependent manner. The ability of CG-16 to activate H2O2 generation by human peripheral blood neutrophils was primed by the Ca2+-ionophor ionomycin and by cytochalasin B. In a general context, these results emphasize that – besides plant lectins as laboratory tools – animal lectins can trigger cell reaction cascades, implying potential in vivo relevance for the measured activities. Within the family of galectins, the activity profiles depend on the target cell type and the individual galectin. Notably, proto-type galectins do not necessarily share a uniform capacity as elicitor. 相似文献
66.
Formation of three-dimensional protein-lipid aggregates in monolayer films induced by surfactant protein B 下载免费PDF全文
This study focuses on the structural organization of surfactant protein B (SP-B) containing lipid monolayers. The artificial system is composed of the saturated phospholipids dipalmitoylphosphatidylcholine (DPPC) and dipalmitoylphosphatidylglycerol (DPPG) in a molar ratio of 4:1 with 0.2 mol% SP-B. The different "squeeze-out" structures of SP-B were visualized by scanning probe microscopy and compared with structures formed by SP-C. Particularly, the morphology and material properties of mixed monolayers containing 0.2 mol% SP-B in a wide pressure range of 10 to 54 mN/m were investigated revealing that filamentous domain boundaries occur at intermediate surface pressure (15-30 mN/m), while disc-like protrusions prevail at elevated pressure (50-54 mN/m). In contrast, SP-C containing lipid monolayers exhibit large flat protrusions composed of stacked bilayers in the plateau region (app. 52 mN/m) of the pressure-area isotherm. By using different scanning probe techniques (lateral force microscopy, force modulation, phase imaging) it was shown that SP-B is dissolved in the liquid expanded rather than in the liquid condensed phase of the monolayer. Although artificial, the investigation of this system contributes to further understanding of the function of lung surfactant in the alveolus. 相似文献
67.
The interaction between Urtica dioica agglutinin (UDA) and N-acetylglucosamine (GlcNAc) and its (1-4)-linked oligomers was studied by fluorescence titration and isothermal titration microcalorimetry. UDA possesses one significant binding site that can be measured calorimetrically. This site is composed of three subsites, each subsite accommodating one GlcNAc residue. The interaction is enthalpically driven, and the binding area of UDA is characterized by a H of interaction for a given oligosaccharide considerably smaller than that of wheat germ agglutinin (WGA), despite the fact that they both belong to a family of proteins composed entirely of hevein domains. Relatively high Cp values of the UDA-carbohydrate interactions and more favorable entropy term compared to WGA suggest that binding of the carbohydrate ligands by UDA has a higher hydrophobic component than that of WGA. 相似文献
68.
Mohamed Abd El Rahman Denise Haase Axel Rentzsch Julia Olchvary Hans-Joachim Sch?fers Wolfram Henn Stefan Wagenpfeil Hashim Abdul-Khaliq 《PloS one》2015,10(4)
Background
In asymptomatic Marfan syndrome (MFS) patients we evaluated the relationship between the types of fibrillin-1 (FBN1) gene mutation and possible altered left ventricular (LV) function as assessed by three-dimensional speckle tracking echocardiography (3D-STE).Methods and Results
Forty-five MFS patients (mean age 24±15 years) and 40 age-matched healthy controls were studied. Genetic evaluation for the FBN1 gene was carried on 32 MFS patients. Gene mutation (n = 15, 47%) was classified as mild when the mutation resulted in nearly normally functioning protein, while mutations resulting in abnormally function protein were considered to be severe (n = 17, 53%). All patients and controls underwent 3D-STE for evaluation of LV function by an echocardiographer blinded to the results of the genetic testing. Compared to controls, MFS patients had significantly lower 3D-STE derived LV ejection fraction (EF, 57.43±7.51 vs. 62.69±4.76%, p = 0.0001), global LV longitudinal strain (LS, 14.85±2.89 vs. 17.90±2.01%, p = 0.0001), global LV circumferential strain (CS, 13.93±2.81 vs. 16.82±2.17%, p = 0.0001) and global LV area strain (AS, 25.76±4.43 vs. 30.51±2.61%, p = 0.0001). Apart from the global LV LS all these parameters were significantly lower in patients with severe gene mutation than in those with mild mutation (p<0.05). In the multivariate linear regression analysis only the type of mutation had a significant influence on the 3D-STE derived LVEF (p = 0.017), global CS (p = 0.005) and global AS (p = 0.03).Conclusions
In asymptomatic MFS patients latent LV dysfunction can be detected using 3D STE. The LV dysfunction is mainly related to the severity of gene mutation, suggesting possible primary cardiomyopathy in MFS patients. 相似文献69.
70.
Werner Nachtigall und Hans-Joachim Rothe 《Journal of Ornithology》1982,123(4):439-443
Zusammenfassung Bei Haustauben, die in einem horizontalen Windkanal mit 48 km/h stationär flogen, wurden mit Hilfe von Zeitlupenanalysen Schlagphasen nachgewiesen, die dem vonWeis-Fogh (1973) geforderten clap-and-fling Mechanismus entsprechen. Am Ende des Aufschlags schlagen die beiden Flügel mit der morphologischen Oberseite ± vollständig zusammen (clap). Vor dem Abschlag öffnen sie sich wie die Seiten eines Buches von vorn nach hinten (fling); erst am Ende dieser Phase entfernen sie sich voneinander. Weitere feinkinematische Ergebnisse werden mitgeteilt. Diese instationären Schlagphasen werden insbesondere dann eingesetzt, wenn hohe Luftkräfte benötigt werden. Die Kinematik der Flügelbewegung ist demnach so beschaffen, daß durch frühzeitige Zirkulationsinduzierung bereits ganz zu Beginn des Abschlags hohe Auftriebskräfte erzeugt werden könnten. Es wird diskutiert, daß der clap-and-fling Mechanismus auch für rasche Beschleunigungen bei hohem Schubbedarf eingesetzt werden könnte.
Mit Geräteunterstützung durch die Deutsche Forschungsgemeinschaft 相似文献
Evidence for a clap-and-fling mechanism in pigeons flying in a windtunnel
Summary Slow motion pictures of pigeons flying horizontally at a speed of 48 km/h in a windtunnel have shown flight patterns which seemed to be similar to the clap-and-fling mechanism discribed byWeis-Fogh (1973) for small insects. At the end of upstroke, both upper surfaces of the wings come together ± completely (clap). Before downstroke, the wings are opened like the pages of a book (fling). This instationary wingbeat pattern is used especially when high aerodynamic forces are needed. The clap-and-fling mechanism enables the bird to establish an early circulation so that, at the very beginning of downstroke, high lift forces can be produced. The question whether the clap-and-fling mechanism is also used for quick accelerations when greater thrust is required is also discussed.
Mit Geräteunterstützung durch die Deutsche Forschungsgemeinschaft 相似文献