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991.
992.
Petrillo G Mariggiò MA Aiello C Cordazzo C Fenoglio C Morganti S Croce M Rizzato E Spinelli D Maccagno M Bianchi L Prevosto C Tavani C Viale M 《Bioorganic & medicinal chemistry》2008,16(1):240-247
On the grounds of previous encouraging results on the antitumor activity of (1E,3E)-1,4-bis(1-naphthyl)-2,3-dinitro-1,3-butadiene (1), we have designed and synthesized two new molecules [(1E,3E)-1,4-bis(4-carboxy-1-naphthyl)-2,3-dinitro-1,3-butadiene (2) and methyl (2Z,4E)-2-methylsulfanyl-5-(1-naphthyl)-4-nitro-2,4-pentadienoate (3)] characterized by a common naphthylnitrobutadiene array but with different structural properties, with the aim of approaching to some structure-activity correlation. When 2 and 3 were analyzed in vitro for their inhibition of cell proliferation and pro-apoptotic properties, the carboxyderivative 2 did not furnish appreciable results. In contrast, 3 (which contains only one of the two naphthylnitroethenyl moieties of the original compound 1) showed remarkable activities in the range of micromolar concentrations (in six over eight cell lines its IC(50)s are in the 1-3 microM range), with a significant improvement compared to 1. In particular, 3 proved able to bind to DNA, to upregulate p53, to block cells in the G2/M phase of their cycle, and to induce apoptosis. Thus, very interestingly, the performance of 3 with respect to 1 shows that a single 1-(1-naphthyl)-2-nitroethene moiety is able to ensure better (on four out of eight of the cell lines tested) or comparable levels of activity. This result suggests that the 'molecular-simplification strategy' could furnish a useful instrument for future design in our antitumor research. 相似文献
993.
Dei S Bellucci C Buccioni M Ferraroni M Guandalini L Manetti D Marucci G Matucci R Nesi M Romanelli MN Scapecchi S Teodori E 《Bioorganic & medicinal chemistry》2008,16(10):5490-5500
Completing a long-lasting research on 1,3-oxathiolane muscarinic ligands, we have synthesized a set of isomeric 1-methyl-2-(2,2-alkylaryl-1,3-oxathiolan-5-yl)pyrrolidine 3-sulfoxide derivatives, containing three or four stereogenic centers. In general the compounds are very potent antagonists even if, unlike the corresponding agonists, they show modest subtype selectivity. 相似文献
994.
Sugni M Manno V Barbaglio A Mozzi D Bonasoro F Tremolada P Candia Carnevali MD 《Cell biology and toxicology》2008,24(6):573-586
Echinoderms are valuable test species in marine ecotoxicology and offer a wide range of biological processes appropriate for
this approach. Regenerating echinoderms can be regarded as amenable experimental models for testing the effects of exposure
to contaminants, particularly endocrine disrupter compounds (EDCs). As regeneration is a typical developmental process, physiologically
regulated by humoral mechanisms, it is highly susceptible to the action of pseudo-hormonal contaminants which appear to be
obvious candidates for exerting deleterious actions. In our laboratory experiments, selected EDCs suspected for their antiandrogenic
action (p,p′-DDE and cyproterone acetate) were tested at low concentrations on regenerating specimens of the crinoid Antedon mediterranea. An integrated approach which combines exposure experiments and different morphological analyses was employed; the obtained
results suggest an overall pattern of plausible endocrine disruption in the exposed samples, showing that processes such as
regenerative growth, histogenesis, and differentiation are affected by the exposure to the selected compounds. These results
confirm that (1) regenerative phenomena of echinoderms can be considered valuable alternative models to assess the effects
of exposure to exogenous substances such as EDCs, and (2) these compounds significantly interfere with fundamental processes
of developmental physiology (proliferation, differentiation, etc…) plausibly via endocrine alterations. In terms of future
prospects, taking into account the increasing need to propose animal models different from vertebrates, echinoderms represent
a group on which ecotoxicological studies should be encouraged and specifically addressed. 相似文献
995.
Tessari P Kiwanuka E Vettore M Barazzoni R Zanetti M Cecchet D Orlando R 《American journal of physiology. Gastrointestinal and liver physiology》2008,295(3):G598-G604
We explored the mechanism(s) of increased aromatic amino acids concentrations in liver cirrhosis using phenylalanine (Phe) and tyrosine (Tyr) isotope infusions in male patients with compensated cirrhosis (five in Child Class A, three in B) and in eight matched healthy controls, in both postabsorptive and fed states. After a baseline period, a standard liquid mixed meal was fed continuously over 4 h. Both a "plasma" and an intracellular model were employed. In the patients, steady-state Phe and Tyr concentrations were approximately 30-50% greater, and rates of Phe appearance (Ra) (plasma model), Tyr Ra, and Phe hydroxylation (Hy; both models) were approximately 25 to >100% greater than in controls in both states. Meal ingestion increased (P<0.05 or less vs. basal) Phe and Tyr concentrations, Phe and Tyr Ra, Phe Hy, and % Tyr Ra not deriving from Hy in both groups. Hy and Tyr Ra remained>50% greater (P<0.04 to P<0.01) in patients, whereas Phe Ra was more modestly increased. Phe utilization for protein synthesis increased similarly in both groups. Tyr clearance was normal, whereas Phe clearance tended to be lower (P=0.09, intracellular model) in the patients. In summary, in compensated liver cirrhosis studied under fasted and fed states, 1) Tyr Ra is increased; 2) Phe Hy and Phe Ra (plasma model) are increased; 3) Tyr clearance is normal; and 4) Phe clearance is slightly decreased. In conclusion, in cirrhosis increased total tyrosine Ra and hydroxylation contribute to fasting and postmeal hypertyrosinemia, whereas the mechanism(s) responsible for the hyperphenylalaninemia may include both increased production and decreased disposal. 相似文献
996.
997.
998.
Evaluation of the anti-tuberculosis activity generated by different multigene DNA vaccine constructs
Sali M Clarizio S Pusceddu C Zumbo A Pecorini G Rocca S Zanetti S Delogu G Fadda G 《Microbes and infection / Institut Pasteur》2008,10(6):605-612
Development of multigenic constructs expressing Mycobacterium tuberculosis (Mtb) antigens may be a strategy to obtain improved DNA vaccines against tuberculosis (TB). Several multigenic constructs expressing two or three Mtb antigens as fusion proteins were developed, both as tPA- and ubiquitin-fusion proteins. To demonstrate proper protein expression and intracellular turnover all multiantigens were tagged with the HA epitope and constructs were used to transfect rhabdomyosarcoma (RD) cells. Antigen expression was demonstrated by immunofluorescence using anti-HA antibodies. C57Bl/6 mice were immunized with selected constructs and protective activity was assessed following aerogenic challenge with Mtb. Several of these constructs induced a significant level of protection in the lung and in the spleen. Immunization with the construct expressing tPA85B-ES6 induced a level of protection that approached that provided by BCG. Immunization with a combination of these constructs induced levels of protection that were not superior to those elicited by a single combination, and immunization with a construct expressing five Mtb antigens could not provide an improved level of protection compared to tPA85B-ES6. We conclude that the activity of a DNA vaccine based on tPA85B-ES6 cannot be enhanced by broadening the antigen repertoire with other highly immunogenic secreted Mtb proteins. 相似文献
999.
Vajda I van Pelt J Wolters P Chiappalone M Martinoia S van Someren E van Ooyen A 《Biophysical journal》2008,94(12):5028-5039
Reverberating spontaneous synchronized brain activity is believed to play an important role in neural information processing. Whether and how external stimuli can influence this spontaneous activity is poorly understood. Because periodic synchronized network activity is also prominent in in vitro neuronal cultures, we used cortical cultures grown on multielectrode arrays to examine how spontaneous activity is affected by external stimuli. Spontaneous network activity before and after low-frequency electrical stimulation was quantified in several ways. Our results show that the initially stable pattern of stereotypical spontaneous activity was transformed into another activity pattern that remained stable for at least 1 h. The transformations consisted of changes in single site and culture-wide network activity as well as in the spatiotemporal dynamics of network bursting. We show for the first time that low-frequency electrical stimulation can induce long-lasting alterations in spontaneous activity of cortical neuronal networks. We discuss whether the observed transformations in network activity could represent a switch in attractor state. 相似文献
1000.
Fruscione F Sturla L Duncan G Van Etten JL Valbuzzi P De Flora A Di Zanni E Tonetti M 《The Journal of biological chemistry》2008,283(1):184-193
GDP-D-mannose 4,6-dehydratase (GMD) is a key enzyme involved in the synthesis of 6-deoxyhexoses in prokaryotes and eukaryotes. Paramecium bursaria chlorella virus-1 (PBCV-1) encodes a functional GMD, which is unique among characterized GMDs because it also has a strong stereospecific NADPH-dependent reductase activity leading to GDP-D-rhamnose formation (Tonetti, M., Zanardi, D., Gurnon, J., Fruscione, F., Armirotti, A., Damonte, G., Sturla, L., De Flora, A., and Van Etten, J.L. (2003) J. Biol. Chem. 278, 21559-21565). In the present study we characterized a recombinant GMD encoded by another chlorella virus, Acanthocystis turfacea chlorella virus 1 (ATCV-1), demonstrating that it has the expected dehydratase activity. However, it also displayed significant differences when compared with PBCV-1 GMD. In particular, ATCV-1 GMD lacks the reductase activity present in the PBCV-1 enzyme. Using recombinant PBCV-1 and ATCV-1 GMDs, we determined that the enzymatically active proteins contain tightly bound NADPH and that NADPH is essential for maintaining the oligomerization status as well as for the stabilization and function of both enzymes. Phylogenetic analysis indicates that PBCV-1 GMD is the most evolutionary diverged of the GMDs. We conclude that this high degree of divergence was the result of the selection pressures that led to the acquisition of new reductase activity to synthesize GDP-D-rhamnose while maintaining the dehydratase activity in order to continue to synthesize GDP-L-fucose. 相似文献