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61.
Jakub Hofman Radim Ku?era Daniela Cihalova Jiri Klimes Martina Ceckova Frantisek Staud 《PloS one》2013,8(10)
Purine cyclin-dependent kinase inhibitors have been recognized as promising candidates for the treatment of various cancers; nevertheless, data regarding interaction of these substances with drug efflux transporters is still lacking. Recently, we have demonstrated inhibition of breast cancer resistance protein (ABCG2) by olomoucine II and purvalanol A and shown that these compounds are able to synergistically potentiate the antiproliferative effect of mitoxantrone, an ABCG2 substrate. In this follow up study, we investigated whether olomoucine II and purvalanol A are transported by ABCG2 and ABCB1 (P-glycoprotein). Using monolayers of MDCKII cells stably expressing human ABCB1 or ABCG2, we demonstrated that olomoucine II, but not purvalanol A, is a dual substrate of both ABCG2 and ABCB1. We, therefore, assume that pharmacokinetics of olomoucine II will be affected by both ABCB1 and ABCG2 transport proteins, which might potentially result in limited accumulation of the compound in tumor tissues or lead to drug-drug interactions. Pharmacokinetic behavior of purvalanol A, on the other hand, does not seem to be affected by either ABCG2 or ABCB1, theoretically favoring this drug in the potential treatment of efflux transporter-based multidrug resistant tumors. In addition, we observed intensive sulfatation of olomoucine II in MDCKII cell lines with subsequent active efflux of the metabolite out of the cells. Therefore, care should be taken when performing pharmacokinetic studies in MDCKII cells, especially if radiolabeled substrates are used; the generated sulfated conjugate may largely contaminate pharmacokinetic analysis and result in misleading interpretation. With regard to chemical structures of olomoucine II and purvalanol A, our data emphasize that even drugs with remarkable structure similarity may show different pharmacokinetic behavior such as interactions with ABC transporters or biotransformation enzymes. 相似文献
62.
Daniela Zappi 《Curtis's Botanical Magazine》1993,10(4):166-170
63.
Elmar Porten Beate Seliger Verena A. Schneider Stefan W?ll Daniela Stangel Rene Ramseger Stephan Kr?ger 《The Journal of biological chemistry》2010,285(5):3114-3125
Clustering or overexpression of the transmembrane form of the extracellular matrix proteoglycan agrin in neurons results in the formation of numerous highly motile filopodia-like processes extending from axons and dendrites. Here we show that similar processes can be induced by overexpression of transmembrane-agrin in several non-neuronal cell lines. Mapping of the process-inducing activity in neurons and non-neuronal cells demonstrates that the cytoplasmic part of transmembrane agrin is dispensable and that the extracellular region is necessary for process formation. Site-directed mutagenesis reveals an essential role for the loop between β-sheets 3 and 4 within the Kazal subdomain of the seventh follistatin-like domain of TM-agrin. An aspartic acid residue within this loop is critical for process formation. The seventh follistatin-like domain could be functionally replaced by the first and sixth but not by the eighth follistatin-like domain, demonstrating a functional redundancy among some follistatin-like domains of agrin. Moreover, a critical distance of the seventh follistatin-like domain to the plasma membrane appears to be required for process formation. These results demonstrate that different regions within the agrin protein are responsible for synapse formation at the neuromuscular junction and for process formation in central nervous system neurons and suggest a role for agrin''s follistatin-like domains in the developing central nervous system. 相似文献
64.
A possible method of finding the best concentration of a chemical mutagen or a shortterm action is demonstrated by the results
obtained withChlamydomonas geitleri. Mostly two cases occur. We must either use the shortest time of the mutagen action with a sufficiently high effect or utilize
the whole limited time for this action using a suitable concentration with a similar effect. It is possible to choose such
a structure of the doae of the chemical mutagen which in the mutation spectrum ensures either the optimal frequencies of all
components or of only some of them chosen beforehand. 相似文献
65.
Ferruccio Berti Claudio Omini Daniela Longiave 《Prostaglandins & other lipid mediators》1977,14(2):241-249
The horse-chestnut saponin Aescin, an anti-exudative compound, induces contraction of isolated portal vein of rat and rabbit. This effect appears to be mediated by Prostaglandins of Fα type.The ability of Aescin to stimulate generation and release of Prostaglandins has been demonstrated in isolated lung of the rat. Mass-fragmentographic analysis of the lung effluent indicate that when Aescin is perfused through this organ the release of PGF2α is increased. The capability of Aescin to generate Prostaglandins is discussed in connection with its anti-exudative activity. 相似文献
66.
Patricia Kabitzke Diana Morales Dansha He Kimberly Cox Jane Sutphen Lucinda Thiede Emily Sabath Taleen Hanania Barbara Biemans Daniela Brunner 《Genes, Brain & Behavior》2020,19(7)
Phenotyping mouse model systems of human disease has proven to be a difficult task, with frequent poor inter‐ and intra‐laboratory replicability, particularly in behavioral domains such as social and cognitive function. However, establishing robust animal model systems with strong construct validity is of fundamental importance as they are central tools for understanding disease pathophysiology and developing therapeutics. To complete our studies of mouse model systems relevant to autism spectrum disorder (ASD), we present a replication of the main findings from our two published studies of five genetic mouse model systems of ASD. To assess the intra‐laboratory robustness of previous results, we chose the two model systems that showed the greatest phenotypic differences, the Shank3/F and Cntnap2, and repeated assessments of general health, activity and social behavior. We additionally explored all five model systems in the same framework, comparing all results obtained in this three‐yearlong effort using informatics techniques to assess commonalities and differences. Our results showed high intra‐laboratory replicability of results, even for those with effect sizes that were not particularly large, suggesting that discrepancies in the literature may be dependent on subtle but pivotal differences in testing conditions, housing enrichment, or background strains and less so on the variability of the behavioral phenotypes. The overall informatics analysis suggests that in our behavioral assays we can separate the set of tested mouse model system into two main classes that in some aspects lie on opposite ends of the behavioral spectrum, supporting the view that autism is not a unitary concept. 相似文献
67.
Simon Borna Ales Drobek Jarmila Kralova Daniela Glatzova Iva Splichalova Matej Fabisik Jana Pokorna Tereza Skopcova Pavla Angelisova Veronika Kanderova Julia Starkova Petr Stanek Orest V. Matveichuk Nataliia Pavliuchenko Katarzyna Kwiatkowska Majd B. Protty Michael G. Tomlinson Meritxell Alberich‐Jorda Vladimir Korinek Tomas Brdicka 《Journal of cellular and molecular medicine》2020,24(2):1980-1992
WW domain binding protein 1‐like (WBP1L), also known as outcome predictor of acute leukaemia 1 (OPAL1), is a transmembrane adaptor protein, expression of which correlates with ETV6‐RUNX1 (t(12;21)(p13;q22)) translocation and favourable prognosis in childhood leukaemia. It has a broad expression pattern in haematopoietic and in non‐haematopoietic cells. However, its physiological function has been unknown. Here, we show that WBP1L negatively regulates signalling through a critical chemokine receptor CXCR4 in multiple leucocyte subsets and cell lines. We also show that WBP1L interacts with NEDD4‐family ubiquitin ligases and regulates CXCR4 ubiquitination and expression. Moreover, analysis of Wbp1l‐deficient mice revealed alterations in B cell development and enhanced efficiency of bone marrow cell transplantation. Collectively, our data show that WBP1L is a novel regulator of CXCR4 signalling and haematopoiesis. 相似文献
68.
69.
Afforestation of formerly open landscapes can transform mammalian predator communities, potentially impacting prey species like ground‐nesting birds. In Scotland's Flow Country, a globally important peatland containing many forestry plantations, earlier studies found reduced densities of breeding waders on open bogs, when forestry plantations were present within 700 m. One plausible explanation for this pattern is mammalian predation. We tested whether mammalian predator indices, based on scats (feces), differed between (1) open bog, forestry plantations, and former plantations being restored as bog (“restoration” habitats); (2) restoration habitats of different ages; and (3) open bogs with differing amounts of nearby forestry. We measured summer scat density and size over 14 years in 26 transects 0.6–4.5 km in length, collecting data during 93, 96, and 79 transect‐years in bog, forestry, and restoration habitats respectively. In forestry, scat density increased eightfold, reaching values ~6 times higher than those of bogs. On open bogs with over 10% forestry within 700 m, scat densities were 2.9 times higher than on open bogs with less forestry nearby. Results support the hypothesis that mammalian predators might be responsible for the low densities of breeding waders close to forests, on adjacent open bogs. In restoration habitats, scat densities rose 6–10 years after felling but fell to levels similar to open bogs in older restoration habitats, supporting restoration management as a means of reducing mammalian predator activity/abundance. We urge caution around decisions to establish forestry plantations in open landscapes of high biodiversity importance. 相似文献
70.
Muriel Cario Catherine Pain Priscilla Kaulanjan‐Checkmodine Daniela Masia Gabriele Delia Vincent Casoli Pierre Costet Jean‐Franois Goussot Vronique Guyonnet‐Duperat Alice Bibeyran Khaled Ezzedine Corinne Reymermier Valrie Andre‐Frei Alain Taieb 《Pigment cell & melanoma research》2020,33(3):435-445
Human skin melanin pigmentation is regulated by systemic and local factors. According to the type of melanin produced by melanocytes, the transfer and degradation of melanosomes differ, thus accounting for most variations between ethnicities. We made the surprising observation that in a drastically changed environment, white and black phenotypes are reversible since Caucasian skin grafted onto nude mice can become black with all black phenotypic characteristics. Black xenografts differed essentially from other grafts by the levels of epidermal FGF‐2 and keratin 5. In vitro analysis confirmed that FGF‐2 directly regulates keratin 5. Interestingly, this phenomenon may be involved in human pathology. Keratin 5 mutations in Dowling–Degos Disease (DDD) have already been associated with the pheomelanosome–eumelanosome transition. In a DDD patient, keratin 5 was expressed in the basal and spinous layers, as observed in black xenografts. Furthermore, in a common age‐related hyperpigmentation disorder like senile lentigo (SL), keratin 5 distribution is also altered. In conclusion, modulation of keratin 5 expression and distribution either due to mutations or factors may account for the development of pigmentary disorders. 相似文献