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31.
Anna Ghelli Anna Maria Porcelli Claudia Zanna Sara Vidoni Stefano Mattioli Anna Barbieri Luisa Iommarini Maria Pala Alessandro Achilli Antonio Torroni Michela Rugolo Valerio Carelli 《PloS one》2009,4(11)
Leber''s hereditary optic neuropathy (LHON) is a maternally inherited blinding disease due to mitochondrial DNA (mtDNA) point mutations in complex I subunit genes, whose incomplete penetrance has been attributed to both genetic and environmental factors. Indeed, the mtDNA background defined as haplogroup J is known to increase the penetrance of the 11778/ND4 and 14484/ND6 mutations. Recently it was also documented that the professional exposure to n-hexane might act as an exogenous trigger for LHON. Therefore, we here investigate the effect of the n-hexane neurotoxic metabolite 2,5-hexanedione (2,5-HD) on cell viability and mitochondrial function of different cell models (cybrids and fibroblasts) carrying the LHON mutations on different mtDNA haplogroups. The viability of control and LHON cybrids and fibroblasts, whose mtDNAs were completely sequenced, was assessed using the MTT assay. Mitochondrial ATP synthesis rate driven by complex I substrates was determined with the luciferine/luciferase method. Incubation with 2,5-HD caused the maximal loss of viability in control and LHON cells. The toxic effect of this compound was similar in control cells irrespective of the mtDNA background. On the contrary, sensitivity to 2,5-HD induced cell death was greatly increased in LHON cells carrying the 11778/ND4 or the 14484/ND6 mutation on haplogroup J, whereas the 11778/ND4 mutation in association with haplogroups U and H significantly improved cell survival. The 11778/ND4 mutation on haplogroup U was also more resistant to inhibition of complex I dependent ATP synthesis by 2,5-HD. In conclusion, this study shows that mtDNA haplogroups modulate the response of LHON cells to 2,5-HD. In particular, haplogroup J makes cells more sensitive to its toxic effect. This is the first evidence that an mtDNA background plays a role by interacting with an environmental factor and that 2,5-HD may be a risk element for visual loss in LHON. This proof of principle has broad implications for other neurodegenerative disorders such as Parkinson''s disease. 相似文献
32.
Debiaggi M Canducci F Terulla C Sampaolo M Marinozzi MC Alessandrino PE Colombo AA Caldera D Bragotti LZ Migliavacca R Bianchi E Romero E Clementi M 《The new microbiologica》2007,30(3):255-258
From October 2004 through October 2006 a study was performed to evaluate the prevalence of human Metapneumovirus (hMPV) infection in adult hematopoietic stem cell transplant (HSCT) recipients. Sequential nasopharyngeal aspirates (NPA) were collected independently from respiratory symptoms and evaluated for hMPV-RNA by polymerase chain reaction (PCR) and sequence analysis. Results indicate epidemiological and molecular differences between the 2004-2005 and 2005-2006 periods and that hMPV seems not to symptomatically affect HSCT patients or cause late respiratory sequelae. In addition, data collected suggest a hospital origin of hMPV infection in most HSCT patients during the 2004-2005 period. 相似文献
33.
The antibody-mediated targeted delivery of cytokines to sites of disease is a promising avenue for cancer therapy, but it
is largely unexplored for the treatment of chronic inflammatory conditions. Using both radioactive and fluorescent techniques,
the human monoclonal antibodies L19 and G11 (specific to two markers of angiogenesis that are virtually undetectable in normal
adult tissues) were found to selectively localize at arthritic sites in the murine collagen-induced model of rheumatoid arthritis
following intravenous (i.v.) administration. The same animal model was used to study the therapeutic action of the L19 antibody
fused to the cytokines IL-2, tumour necrosis factor (TNF) and IL-10. Whereas L19–IL-2 and L19–TNF treatment led to increased
arthritic scores and paw swellings, the fusion protein L19–IL-10 displayed a therapeutic activity, which was superior to the
activity of IL-10 fused to an antibody of irrelevant specificity in the mouse. The anti-inflammatory cytokine IL-10 has been
investigated for the treatment of patients with rheumatoid arthritis, but clinical development plans have been discontinued
because of a lack of efficacy. Because the antigen recognised by L19 is strongly expressed at sites of arthritis in humans
and identical in both mice and humans, it suggests that the fusion protein L19–IL-10 might help overcome some of the clinical
limitations of IL-10 and provide a therapeutic benefit to patients with chronic inflammatory disorders, including arthritis. 相似文献
34.
Michela Flego Alessandro Ascione Silvia Zamboni Maria L Dupuis Valentina Imperiale Maurizio Cianfriglia 《BMC biotechnology》2007,7(1):38
Background
A hallmark of prion disease is the transformation of normal cellular prion protein (PrPc) into an infectious disease-associated isoform, (PrPsc). Anti-prion protein monoclonal antibodies are invaluable for structure-function studies of PrP molecules. Furthermore recent in vitro and in vivo studies indicate that anti-PrP monoclonal antibodies can prevent the incorporation of PrPc into propagating prions. 相似文献35.
Cifoni Marco Boggero Angela Rogora Michela Ciampittiello Marzia Martnez Alejandro Galassi Diana Maria Paola Fiasca Barbara Di Lorenzo Tiziana 《Hydrobiologia》2022,849(16):3545-3564
Hydrobiologia - Human-induced water level fluctuations (WLFs) are among the major pressures threatening lake ecosystems. Their effect on meiobenthic species of the littoral zone has been... 相似文献
36.
Patrilineal populations show more male transmission of reproductive success than cognatic populations in Central Asia,which reduces their genetic diversity 下载免费PDF全文
37.
Dimitra Gkika Loic Lemonnier George Shapovalov Dmitri Gordienko Céline Poux Michela Bernardini Alexandre Bokhobza Gabriel Bidaux Cindy Degerny Kathye Verreman Basma Guarmit Mohamed Benahmed Yvan de Launoit Rene J.M. Bindels Alessandra Fiorio Pla Natalia Prevarskaya 《The Journal of cell biology》2015,208(1):89-107
TRPM8 is a cold sensor that is highly expressed in the prostate as well as in other non-temperature-sensing organs, and is regulated by downstream receptor–activated signaling pathways. However, little is known about the intracellular proteins necessary for channel function. Here, we identify two previously unknown proteins, which we have named “TRP channel–associated factors” (TCAFs), as new TRPM8 partner proteins, and we demonstrate that they are necessary for channel function. TCAF1 and TCAF2 both bind to the TRPM8 channel and promote its trafficking to the cell surface. However, they exert opposing effects on TRPM8 gating properties. Functional interaction of TCAF1/TRPM8 also leads to a reduction in both the speed and directionality of migration of prostate cancer cells, which is consistent with an observed loss of expression of TCAF1 in metastatic human specimens, whereas TCAF2 promotes migration. The identification of TCAFs introduces a novel mechanism for modulation of TRPM8 channel activity. 相似文献
38.
Engineering temporal accumulation of a low recalcitrance polysaccharide leads to increased C6 sugar content in plant cell walls 下载免费PDF全文
Miguel E. Vega‐Sánchez Dominique Loqué Jeemeng Lao Michela Catena Yves Verhertbruggen Thomas Herter Fan Yang Jesper Harholt Berit Ebert Edward E. K. Baidoo Jay D. Keasling Henrik V. Scheller Joshua L. Heazlewood Pamela C. Ronald 《Plant biotechnology journal》2015,13(7):903-914
Reduced cell wall recalcitrance and increased C6 monosaccharide content are desirable traits for future biofuel crops, as long as these biomass modifications do not significantly alter normal growth and development. Mixed‐linkage glucan (MLG), a cell wall polysaccharide only present in grasses and related species among flowering plants, is comprised of glucose monomers linked by both β‐1,3 and β‐1,4 bonds. Previous data have shown that constitutive production of MLG in barley (Hordeum vulgare) severely compromises growth and development. Here, we used spatio‐temporal strategies to engineer Arabidopsis thaliana plants to accumulate significant amounts of MLG in the cell wall by expressing the rice CslF6 MLG synthase using secondary cell wall and senescence‐associated promoters. Results using secondary wall promoters were suboptimal. When the rice MLG synthase was expressed under the control of a senescence‐associated promoter, we obtained up to four times more glucose in the matrix cell wall fraction and up to a 42% increase in saccharification compared to control lines. Importantly, these plants grew and developed normally. The induction of MLG deposition at senescence correlated with an increase of gluconic acid in cell wall extracts of transgenic plants in contrast to the other approaches presented in this study. MLG produced in Arabidopsis has an altered structure compared to the grass glucan, which likely affects its solubility, while its molecular size is unaffected. The induction of cell wall polysaccharide biosynthesis in senescing tissues offers a novel engineering alternative to enhance cell wall properties of lignocellulosic biofuel crops. 相似文献
39.
Vacca F D'Ambrosi N Nestola V Amadio S Giustizieri M Cucchiaroni ML Tozzi A Velluz MC Mercuri NB Volonté C 《Glycobiology》2011,21(5):634-643
N-Glycosylation affects the function of ion channels at the level of multisubunit assembly, protein trafficking, ligand binding and channel opening. Like the majority of membrane proteins, ionotropic P2X receptors for extracellular ATP are glycosylated in their extracellular moiety. Here, we used site-directed mutagenesis to the four predicted N-glycosylation sites of P2X(3) receptor (Asn(139), Asn(170), Asn(194) and Asn(290)) and performed comparative analysis of the role of N-glycans on protein stability, plasma membrane delivery, trimer formation and inward currents. We have found that in transiently transfected HEK293 cells, Asn(170) is apparently the most important site for receptor stability, since its mutation causes a primary loss in protein content and indirect failure in membrane expression, oligomeric association and inward current responses. Even stronger effects are obtained when mutating Thr(172) in the same glycosylation consensus. Asn(194) and Asn(290) are the most dispensable, since even their simultaneous mutation does not affect any tested receptor feature. All double mutants containing Asn(170) mutation or the Asn(139)/Asn(290) double mutant are instead almost unable to assemble into a functional trimeric structure. The main emerging finding is that the inability to assemble into trimers might account for the impaired function in P2X(3) mutants where residue Asn(170) is replaced. These results improve our knowledge about the role of N-glycosylation in proper folding and oligomeric association of P2X(3) receptor. 相似文献
40.
Bolognesi ML Bartolini M Tarozzi A Morroni F Lizzi F Milelli A Minarini A Rosini M Hrelia P Andrisano V Melchiorre C 《Bioorganic & medicinal chemistry letters》2011,21(9):2655-2658
Memoquin (1) is a lead compound multitargeted against Alzheimer’s disease (AD). It is an AChE inhibitor, free-radical scavenger, and inhibitor of amyloid-β (Aβ) aggregation. A new series of 1 derivatives was designed and synthesized by linking its 2,5-diamino-benzoquinone core with motifs that are present in the structure of known amyloid binding agents like curcumin, the benzofuran derivative SKF64346, or the benzothiazole bearing compounds KHG21834 and BTA-1. The weaker AChE inhibitory potencies and the concomitant nearly equipotent anti-amyloid activities of the new compounds with respect to 1 resulted in a more balanced biological profile against both targets. Selected compounds turned out to be effective Aβ aggregation inhibitors in a cell-based assay. By properly combining two or more distinct pharmacological properties in a molecule, we can achieve greater effectiveness compared to single-targeted drugs for investigating AD. 相似文献