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221.
Wnt/β‐catenin signaling plays a key role in embryonic development, stem cell biology, and neurogenesis. However, the mechanisms of Wnt signal transmission, notably how the receptors are regulated, remain incompletely understood. Here we describe that the Parkinson's disease‐associated receptor GPR37 functions in the maturation of the N‐terminal bulky β‐propellers of the Wnt co‐receptor LRP6. GPR37 is required for Wnt/β‐catenin signaling and protects LRP6 from ER‐associated degradation via CHIP (carboxyl terminus of Hsc70‐interacting protein) and the ATPase VCP. GPR37 is highly expressed in neural progenitor cells (NPCs) where it is required for Wnt‐dependent neurogenesis. We conclude that GPR37 is crucial for cellular protein quality control during Wnt signaling. 相似文献
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223.
Trichosanthin inhibits T cell activation by interfering with the recruitment of ZAP-70 to CD3 ζchain
INTRoDUCTIONThichosanthin(Tk),aplantproteinisolatedfromaChinesemedicinalherbTh-1.Correspondenceaddress:Dr.KuangYenCHoU,ShanghaiInstituteofImmunology,Shang-haiSecondMedicalUniversity28oSouthChongqingRoad,Shanghai2ooo25,China.Fax:(8621)63846383,E-mail:my@sh… 相似文献
224.
In insulin-sensitive 3T3-L1 adipocytes, selenium stimulates glucose transport and antilipolysis and these actions of selenium, like insulin actions, are sensitive to wortmanin, an inhibitor of phosphatidylinositol-3-kinase (PI3K). Selenium stimulates PI3K activity that is sustained up to 24 h. Selenium after 5-10 min increases tyrosine phosphorylation of selective cellular proteins, but after 24 h overall tyrosine phosphorylation is increased. Tyrosine phosphorylation of insulin receptor substrate 1 is detected when enriched by immunoprecipitation with anti-PI3K antibody. Selenium, however, does not stimulate insulin receptor tyrosine kinase activity. Selenium also increases phosphorylation of other insulin signaling proteins, including Akt and extracellular signal regulated kinases. Selenium-stimulated glucose transport is accompanied by increases in glucose transporter-1 content in the plasma membrane. These data are consistent with similar selenium action in glucose transport in 3T3-L1 fibroblasts expressing mainly GLUT1. In chronic insulin-induced insulin resistant cells, selenium unlike insulin fully stimulates glucose transport. In summary, selenium stimulates glucose transport and antilipolysis in a PI3K-dependent manner, but independent of insulin receptor activation. Selenium exerts both insulin-like and non-insulin-like actions in cells. 相似文献
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226.
Ueno Y Shinki T Nagai Y Murayama H Fujii K Suda T 《Journal of cellular biochemistry》2003,90(2):267-277
It is known that pharmacological or toxic doses of vitamin D induce bone resorption both in vivo and in vitro, whereas physiological doses of the vitamin have a protective effect on bone in vivo. To investigate the discrepancies of the dose-dependent effect of vitamin D on bone resorption, we examined the in vivo effect of 1,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)] on the expression of the receptor activator of nuclear factor-kappaB (NF-kappaB) ligand (RANKL) and osteoprotegerin (OPG) mRNAs in bone of thyroparathyroidectomized (TPTX) rats infused with or without parathyroid hormone (PTH). Continuous infusion of 50 ng/h of PTH greatly increased the expression of RANKL mRNA in bone of TPTX rats. Expression of OPG mRNA was not altered by PTH infusion. When graded doses of 1,25(OH)(2)D(3) was daily administered orally for 14 days to normocalcemic TPTX rats constantly infused with PTH, 0.01 and 0.1 microg/kg of 1,25(OH)(2)D(3) inhibited the PTH-induced RANKL mRNA expression, but 0.5 microg/kg of the vitamin did not inhibit it. Regulator of G protein signaling-2 (RGS-2) gene expression was suppressed by 1,25(OH)(2)D(3) dose-dependently, but PTH/PTHrP receptor mRNA expression was not altered. Bone morphometric analyses revealed that 1,25(OH)(2)D(3) suppressed PTH-induced osteoclast number in vivo. These results suggest that pharmacological or toxic doses of 1,25(OH)(2)D(3) stimulate bone resorption by inducing RANKL, but a certain range of physiological doses of the vitamin inhibit PTH-induced bone resorption, the latter mechanism appeared to be mediated, at least in part, by the suppression of the PTH/PTHrP receptor-mediated signaling. 相似文献
227.
Rykx A De Kimpe L Mikhalap S Vantus T Seufferlein T Vandenheede JR Van Lint J 《FEBS letters》2003,546(1):81-86
The protein kinase D family of enzymes consists of three isoforms: PKD1/PKCmu PKD2 and PKD3/PKCnu. They all share a similar architecture with regulatory sub-domains that play specific roles in the activation, translocation and function of the enzymes. The PKD enzymes have recently been implicated in very diverse cellular functions, including Golgi organization and plasma membrane directed transport, metastasis, immune responses, apoptosis and cell proliferation. 相似文献
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229.
Death receptors such as the 55 kDa tumor necrosis factor (TNF) receptor (TNF-R55) or Fas can initiate both apoptotic (caspase-dependent) and caspase-independent routes to programmed cell death (PCD). Here, we demonstrate for the first time that the single murine receptor for (TNF)-related apoptosis-inducing ligand (mTRAIL-R2) can induce a caspase-independent form of PCD with necrosis-like features in addition to apoptosis. Analysis of morphological and cellular features of caspase-independent PCD in response to TRAIL and TNF suggests that mTRAIL-R2 and TNF-R55 elicit caspase-independent PCD through similar pathways, although without participation of cathepsins. Cells overexpressing acid ceramidase (AC), an enzyme that metabolizes the sphingolipid ceramide, show enhanced survival from TRAIL-induced caspase-independent PCD but not from apoptosis, implicating a function of ceramide as a key mediator in caspase-independent PCD (but not apoptosis) induced by mTRAIL-R2. In concert with the enhanced resistance of AC-overexpressing cells against caspase-independent PCD induced by TNF, our results suggest that ceramide acts as a common mediator of caspase-independent PCD caused by death receptors such as mTRAIL-R2 and TNF-R55. 相似文献
230.
Chandra-Shekara AC Gupte M Navarre D Raina S Raina R Klessig D Kachroo P 《The Plant journal : for cell and molecular biology》2006,45(3):320-334
Resistance to Turnip Crinkle Virus (TCV) in Arabidopsis ecotype Dijon (Di)-17 is conferred by the resistance gene HRT and a recessive locus rrt. In Di-17, TCV elicits a hypersensitive response (HR), which is accompanied by increased expression of pathogenesis-related (PR) genes and high levels of salicylic acid (SA). We have previously shown that HRT-mediated resistance to TCV is dependent on SA-mediated signal transduction and that increased levels of SA confer enhanced resistance to TCV via upregulation of the HRT gene. Here we show that HRT-mediated HR and resistance are dependent on light. A dark treatment immediately following TCV inoculation suppressed HR, resistance and activation of the majority of the TCV-induced genes. However, the absence of light did not affect either TCV-induced elevated levels of free SA or the expression of HRT. Interestingly, in the dark, transgenic plants overexpressing HRT showed susceptibility, but overexpression of HRT coupled with high levels of endogenous SA resulted in pronounced resistance. Consistent with these results is the finding that exogenous application of SA prior to TCV inoculation partially overcame the requirement for light. Light was also required for N gene-mediated HR and resistance to Tobacco Mosaic Virus, suggesting that it is an important factor which may be generally required during defense signaling. 相似文献