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81.
Anna CC Aguiar Ananda C Cunha Isabela Penna Ceravolo Regina A Correia Gon?alves Arildo JB Oliveira Antoniana Ursine Krettli 《Memórias do Instituto Oswaldo Cruz》2015,110(7):906-913
Several species of Aspidosperma plants are used to treat diseases in
the tropics, including Aspidosperma ramiflorum, which acts against
leishmaniasis, an activity that is experimentally confirmed. The species, known as
guatambu-yellow, yellow peroba,
coffee-peroba andmatiambu, grows in the Atlantic
Forest of Brazil in the South to the Southeast regions. Through a guided
biofractionation of A. ramiflorum extracts, the plant activity
against Plasmodium falciparum was evaluated in vitro for toxicity
towards human hepatoma G2 cells, normal monkey kidney cells and nonimmortalised human
monocytes isolated from peripheral blood. Six of the seven extracts tested were
active at low doses (half-maximal drug inhibitory concentration < 3.8 µg/mL); the
aqueous extract was inactive. Overall, the plant extracts and the purified compounds
displayed low toxicity in vitro. A nonsoluble extract fraction and one purified
alkaloid isositsirikine (compound 5) displayed high selectivity indexes (SI) (= 56
and 113, respectively), whereas compounds 2 and 3 were toxic (SI < 10). The
structure, activity and low toxicity of isositsirikine in vitro are described here
for the first time in A. ramiflorum, but only the neutral and
precipitate plant fractions were tested for activity, which caused up to 53%
parasitaemia inhibition of Plasmodium berghei in mice with
blood-induced malaria. This plant species is likely to be useful in the further
development of an antimalarial drug, but its pharmacological evaluation is still
required. 相似文献
82.
83.
Shijun Li Min Tan Franceline Juillard Rajesh Ponnusamy Bruno Correia J. Pedro Simas Maria A. Carrondo Colin E. McVey Kenneth M. Kaye 《The Journal of biological chemistry》2015,290(47):28084-28096
Kaposi sarcoma-associated herpesvirus (KSHV) has a causative role in several human malignancies. KSHV latency-associated nuclear antigen (LANA) mediates persistence of viral episomes in latently infected cells. LANA mediates KSHV DNA replication and segregates episomes to progeny nuclei. The structure of the LANA DNA binding domain was recently solved, revealing a positive electrostatic patch opposite the DNA binding surface, which is the site of BET protein binding. Here we investigate the functional role of the positive patch in LANA-mediated episome persistence. As expected, LANA mutants with alanine or glutamate substitutions in the central, peripheral, or lateral portions of the positive patch maintained the ability to bind DNA by EMSA. However, all of the substitution mutants were deficient for LANA DNA replication and episome maintenance. Mutation of the peripheral region generated the largest deficiencies. Despite these deficiencies, all positive patch mutants concentrated to dots along mitotic chromosomes in cells containing episomes, similar to LANA. The central and peripheral mutants, but not the lateral mutants, were reduced for BET protein interaction as assessed by co-immunoprecipitation. However, defects in BET protein binding were independent of episome maintenance function. Overall, the reductions in episome maintenance closely correlated with DNA replication deficiencies, suggesting that the replication defects account for the reduced episome persistence. Therefore, the electrostatic patch exerts a key role in LANA-mediated DNA replication and episome persistence and may act through a host cell partner(s) other than a BET protein or by inducing specific structures or complexes. 相似文献
84.
Patrícia M. Paes de Sousa Sofia R. Pauleta M. Lurdes Simões Gonçalves Graham W. Pettigrew Isabel Moura José J. G. Moura Margarida M. Correia dos Santos 《Journal of biological inorganic chemistry》2011,16(2):209-215
In this work it is demonstrated that the characterization of c-type haem containing proteins by electrochemical techniques needs to be cautiously performed when using pyrolytic graphite
electrodes. An altered form of the cytochromes, which has a redox potential 300 mV lower than that of the native state and
displays peroxidatic activity, can be induced by interaction with the pyrolytic graphite electrode. Proper control experiments
need to be performed, as altered conformations of the enzymes containing c-type haems can show activity towards the enzyme substrate. The work was focused on the study of the activation mechanism
and catalytic activity of cytochrome c peroxidase from Paracoccus
pantotrophus. The results could only be interpreted with the assignment of the observed non-turnover and catalytic signals to a non-native
conformation state of the electron-transferring haem. The same phenomenon was detected for Met–His monohaem cytochromes (mitochondrial
cytochrome c and Desulfovibrio
vulgaris cytochrome c-553), as well as for the bis-His multihaem cytochrome c
3 from Desulfovibrio
gigas, showing that this effect is independent of the axial coordination of the c-type haem protein. Thus, the interpretation of electrochemical signals of c-type (multi)haem proteins at pyrolytic graphite electrodes must be carefully performed, to avoid misassignment of the signals
and incorrect interpretation of catalytic intermediates. 相似文献
85.
Netrins are secreted proteins that were first identified as guidance cues, directing cell and axon migration during neural development. Subsequent findings have demonstrated that netrins can influence the formation of multiple tissues, including the vasculature, lung, pancreas, muscle and mammary gland, by mediating cell migration, cell-cell interactions and cell-extracellular matrix adhesion. Recent evidence also implicates the ongoing expression of netrins and netrin receptors in the maintenance of cell-cell organisation in mature tissues. Here, we review the mechanisms involved in netrin signalling in vertebrate and invertebrate systems and discuss the functions of netrin signalling during the development of neural and non-neural tissues. 相似文献
86.
Mechanical clearing of understory vegetation is increasingly used in Euro-Mediterranean forests to reduce fire hazard, yet
its long-term consequences for biodiversity remain poorly understood. This study analysed the influence of time since understory
management and management frequency, on herbaceous species richness, cover and composition, functional richness and composition,
and richness and cover within functional groups (life and growth forms, dispersal strategy, clonality, and plant height),
using a chronosequence of cork oak (Quercus suber) stands spanning about 70 years. Overall species richness was virtually constant over time, but the richness of species with
annual life form and plasticity in height was much higher in recently and recurrently treated stands; the opposite was found
for perennial (mainly hemicryptophytes and chamaephytes), tussock-forming and clonal species richness, and functional richness.
Overall herbaceous cover and that of annual, semi-basal, non-clonal and plastic species (in height) were favoured by recent
and recurrent fuel treatments; cover by perennial (hemicryptophytes and chamaephytes), short basal, tussock-forming, and clonal
species tended to increase for >10–20 years after management, and declined with management frequency. There was a marked shift
in species and functional composition associated with time since understory management and management frequency. These findings
suggest that widespread fuel management at <10 year intervals may shift understory herb communities to early-successional
stages, impairing the persistence of species and functional groups recovering slowly after disturbance. Fuel management needs
to balance the dual goals of fire hazard reduction and biodiversity conservation, retaining undisturbed patches in landscapes
otherwise managed to reduce fuel accumulation. 相似文献
87.
Sandra Correia Maria Ludovina Lopes Jorge M. Canhoto 《Trees - Structure and Function》2011,25(6):1009-1020
Somatic embryogenesis is a valuable tool for plant breeding. In recent years, different aspects related to somatic embryogenesis
(SE) induction in tamarillo have been studied at our laboratory. In this work, results concerning the establishment of a protocol
for cloning an adult tamarillo tree through SE are presented. Attempts to induce SE in tamarillo from various explants directly
taken from an adult tree were unsuccessful and only calli with no embryogenic potential were initiated. To overcome the lack
of potential of adult tissues for SE, an indirect approach was attempted in which shoots from an adult tree were first established
in vitro and then wounded leaves were used for SE induction. A low rate of embryogenic tissue formation was obtained (19.4%),
but it was in the range of initiation rates from leaf explants of in vitro cloned plantlets of different tamarillo cultivars
(red, orange and yellow) that originated from a single seedling (13.3–54.4%). High variation in SE initiation among juvenile
controls could not be explained by different organogenetic potential, as no significant differences in shoot proliferation
or rooting ability during micropropagation could be detected. Subcultures of embryogenic lines from the adult tree allowed
us to obtain a large amount of embryogenic tissue that, after 8 weeks on a PGR-free medium, gave an average of 111 plants
per gram of fresh mass of embryogenic tissue. A RAPD comparative analysis of somatic embryo-derived plantlets and the donor
tree confirmed that the plantlets had no variation in the DNA regions amplified by 12 primers. These results open the way
for large-scale cloning of elite tamarillo trees through SE. 相似文献
88.
Borroto-Escuela DO Romero-Fernandez W García-Negredo G Correia PA Garriga P Fuxe K Ciruela F 《Cellular physiology and biochemistry》2011,28(5):1009-1022
Acetylcholine challenge produces M(3) muscarinic acetylcholine receptor activation and accessory/scaffold proteins recruitment into a signalsome complex. The dynamics of such a complex is not well understood but a conserved NPxxY motif located within transmembrane 7 and juxtamembrane helix 8 of the receptor was found to modulate G protein activation. Here by means of receptor mutagenesis we unravel the role of the conserved M(3) muscarinic acetylcholine receptor NPxxY motif on ligand binding, signaling and multiprotein complex formation. Interestingly, while a N7.49D receptor mutant showed normal ligand binding properties a N7.49A mutant had reduced antagonist binding and increased affinity for carbachol. Also, besides this last mutant was able to physically couple to Gα(q/11) after carbachol challenge it was neither capable to activate phospholipase C nor phospholipase D. On the other hand, we demonstrated that the Asn-7.49 is important for the interaction between M(3)R and ARF1 and also for the formation of the ARF/Rho/β γ signaling complex, a complex that might determine the rapid activation and desensitization of PLD. Overall, these results indicate that the NPxxY motif of the M(3) muscarinic acetylcholine receptor acts as key conformational switch for receptor signaling and multiprotein complex formation. 相似文献
89.
90.