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991.
Endothelin-1 (ET-1) plays an important role in tissue remodelling and fibrogenesis by inducing synthesis of collagen I via protein kinase C (PKC). ET-1 signals are transduced by two receptor subtypes, the ETA- and ETB-receptors which activate different Galpha proteins. Here, we investigated the expression of both ET-receptor subtypes in human primary dermal fibroblasts and demonstrated that the ETA-receptor is the major ET-receptor subtype expressed. To determine further signalling intermediates, we inhibited Galphai and three phospholipases. Pharmacologic inhibition of Galphai, phosphatidylcholine-phospholipase C (PC-PLC) and phospholipase D (PLD), but not of phospholipase Cbeta, abolished the increase in collagen I by ET-1. Inhibition of all phospholipases revealed similar effects on TGF-beta1 induced collagen I synthesis, demonstrating involvement of PC-PLC and PLD in the signalling pathways elicited by ET-1 and TGF-beta1. ET-1 and TGF-beta1 each stimulated collagen I production and in an additive manner. ET-1 further induced connective tissue growth factor (CTGF), as did TGF-beta1, however, to lower levels. While rapid and sustained CTGF induction was seen following TGF-beta1 treatment, ET-1 increased CTGF in a biphasic manner with lower induction at 3 h and a delayed and higher induction after 5 days of permanent ET-1 treatment. Coincidentally at 5 days of permanent ET-1 stimulation, a switch in ET-receptor subtype expression to the ETB-receptor was observed. We conclude that the signalling pathways induced by ET-1 and TGF-beta1 leading to augmented collagen I production by fibroblasts converge on a similar signalling pathway. Thereby, long-time stimulation by ET-1 resulted in a changed ET-receptor subtype ratio and in a biphasic CTGF induction. 相似文献
992.
Sequence variation within the dominant amino terminus epitope affects antibody binding and neutralization of human immunodeficiency virus type 1 Tat protein 下载免费PDF全文
Ruckwardt TJ Tikhonov I Berg S Hatfield GS Chandra A Chandra P Gilliam B Redfield RR Gallo RC Pauza CD 《Journal of virology》2004,78(23):13190-13196
993.
The uptake of hexoses by Chlorella vulgaris is accompanied by the uptake of protons. For 6-deoxyglucose a stoichiometry of one proton taken up per sugar molecule has been measured, whereas for 1-deoxyglucose approximately two protons are taken up per sugar molecule.It was found that in the presence of 1-deoxyglucose a considerable proportion of “carrier” catalyzes the transport of protons without the concomitant transport of sugar. Presumably the binding of sugar initiates the translocation of the carrier-proton-sugar complex, but whereas 1-deoxyglucose can still dissociate from the complex at the external side of the cytoplasmic membrane, the translocation of the carrier-proton complex continues.This conclusion was reached since (a) the composition of the translocated carrier-proton-sugar complex is the same for both sugar. Its formation is a first order reaction with respect to protons.(b) When 6-deoxyglucose, present inside cells, is exchanged for external sugar, the exchange ratio is two to one when the external sugar is 1-deoxyglucose, two molecules of 6-deoxyglucose are lost for each molecule of 1-deoxyglucose entering. This result indicates that during uptake of 1-deoxyglucose statistically only each second carrier molecule appearing at the internal side of the cytoplasmic membrane is carrying sugar. 相似文献
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996.
Kathrin Davari Samantha Frankenberger Angelika Schmidt Nils-Sebastian Tomi 《Cell cycle (Georgetown, Tex.)》2014,13(23):3659-3669
Maintenance of genome integrity relies on multiple DNA repair pathways as well as on checkpoint regulation. Activation of the checkpoint kinases Chk1 and Chk2 by DNA damage triggers cell cycle arrest and improved DNA repair, or apoptosis in case of excessive damage. Chk1 and Chk2 have been reported to act in a complementary or redundant fashion, depending on the physiological context. During secondary immunoglobulin (Ig) diversification in B lymphocytes, DNA damage is abundantly introduced by activation-induced cytidine deaminase (AID) and processed to mutations in a locus-specific manner by several error-prone DNA repair pathways. We have previously shown that Chk1 negatively regulates Ig somatic hypermutation by promoting error-free homologous recombination and Ig gene conversion. We now report that Chk2 shows opposite effects to Chk1 in the regulation of these processes. Chk2 inactivation in B cells leads to decreased Ig hypermutation and Ig class switching, and increased Ig gene conversion activity. This is linked to defects in non-homologous end joining and increased Chk1 activation upon interference with Chk2 function. Intriguingly, in the context of physiological introduction of substantial DNA damage into the genome during Ig diversification, the 2 checkpoint kinases thus function in an opposing manner, rather than redundantly or cooperatively. 相似文献
997.
Angelika Hesse 《Journal of Ornithology》1988,129(1):83-95
Zusammenfassung Eine neue Familie, die Messelornithidae, die im frühen Tertiär Europas und Nordamerikas verbreitet ist, wird zusammen mit ihrer TypusgattungMesselornis gen. nov. mit der neuen Artcristata spec. nov. beschrieben. Nach osteologischen Kriterien wie Sternumbau und Ausbildung des Quadratum weisen die Messelornithidae nächste Beziehungen zu den Eurypygidae (Sonnenrallen) Südamerikas und nähere Beziehungen zu den Rhynochetidae (Kagus) Neukaledoniens auf. Die Eigenständigkeit der Messelornithidae begründet sich in ihrer besonderen Ausbildung des tarsometatarsalen Hypotarsus sowie der Furcula.
The +Messelornithidae — a new family of the Gruiformes (Aves: Gruiformes: Rhynocheti) of the Tertiary of Europe and Northern America
Summary A new family, the Messelornithidae, which was widespread in the early Tertiary of Europe and Northern America, is described together with its type-genusMesselornis gen. nov. with the new speciescristata spec. nov. The Messelornithidae are closely related to the Eurypygidae (Sunbitterns) of South America and the Rhynochetidae (Kagus) of New Caledonia based on osteological criteria: morphology of the quadrate and structure of the sternum. The Messelornithidae are characterized by the peculiar development of the tarsometatarsal hypotarsus and the furcula.相似文献
998.
Klaus Dose Angelika Bieger-Dose Oliver Kerz Markus Gill 《Origins of life and evolution of the biosphere》1991,21(3):177-187
The inactivation of the anhdrobiotic organismsBacillus subtilis (spores) andDeinococcus radiodurans during long-term exposure (up to several weeks) to extreme dryness (especially vacuum) is correlated with an increase in the number of DNA-strand breaks and other DNA lesions. Survival finally depends on the repair of DNA damages. Exposure of anhydrobiotic organisms to extreme dryness (e.g. on Mars or in space) for geological times will lead to so extended DNA lesions that recovery is extremely unlikely.Presented at the International Symposium on The Biological Exploration of Mars, October 26–27, 1990, Tallahassee, Fl., U.S.A. 相似文献
999.
Dorsal and ventral striatum may differ in their neuronal organisation and function. In a comparative in vitro study, we investigated the release of cholecystokinin-like immunoreactivity from slices of dorsal and ventral striatum, respectively. Release of immunoreactivity was induced by veratridine. The dopamine D2-receptor agonist RU 24926 enhanced, while substance P reduced the release from slices of dorsal striatum. The two agents had no effect on the release of immunoreactivity from slices of ventral striatum. It is concluded that the discrepancy in the modulation of the release of cholecystokinin-like immunoreactivity reflects differences in neuronal organisation in both functionally important areas. 相似文献
1000.
Carina Quast Serena Cuboni Daniel Bader André Altmann Peter Weber Janine Arloth Simone R?h Tanja Brückl Marcus Ising Anna Kopczak Angelika Erhardt Felix Hausch Susanne Lucae Elisabeth B. Binder 《PloS one》2013,8(7)
SLC6A15 is a neuron-specific neutral amino acid transporter that belongs to the solute carrier 6 gene family. This gene family is responsible for presynaptic re-uptake of the majority of neurotransmitters. Convergent data from human studies, animal models and pharmacological investigations suggest a possible role of SLC6A15 in major depressive disorder. In this work, we explored potential functional variants in this gene that could influence the activity of the amino acid transporter and thus downstream neuronal function and possibly the risk for stress-related psychiatric disorders. DNA from 400 depressed patients and 400 controls was screened for genetic variants using a pooled targeted re-sequencing approach. Results were verified by individual re-genotyping and validated non-synonymous coding variants were tested in an independent sample (N = 1934). Nine variants altering the amino acid sequence were then assessed for their functional effects by measuring SLC6A15 transporter activity in a cellular uptake assay. In total, we identified 405 genetic variants, including twelve non-synonymous variants. While none of the non-synonymous coding variants showed significant differences in case-control associations, two rare non-synonymous variants were associated with a significantly increased maximal 3H proline uptake as compared to the wildtype sequence. Our data suggest that genetic variants in the SLC6A15 locus change the activity of the amino acid transporter and might thus influence its neuronal function and the risk for stress-related psychiatric disorders. As statistically significant association for rare variants might only be achieved in extremely large samples (N >70,000) functional exploration may shed light on putatively disease-relevant variants. 相似文献