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101.
Sandrine Théoleyre Damien Masson Marc G. Denis 《Biochemical and biophysical research communications》2010,394(3):453-458
Peroxisome proliferator-activated receptor gamma (PPARγ) ligands have been shown to possess anti-proliferative effects in many types of cancer. In clear cell renal cell carcinoma (CCRCC), the targets involved in these effects are not known. In this study, we demonstrated that, in CCRCC cell lines, the endogenous PPARγ ligand 15-deoxy-Δ12,14-prostaglandin J2 (15dPGJ2) induces the expression, both at the mRNA and the protein levels, of the HtrA3 gene. This gene belongs to the High-Temperature Requirement Factor A family of serine proteases that repress signaling by TGF-β family members and inhibit cell migration. Rosiglitazone or ciglitazone, synthetic PPARγ agonists, did not induce HtrA3 expression, and the PPARγ antagonist GW9662 did not prevent 15dPGJ2 induction, suggesting that the up-regulation of HtrA3 by 15dPGJ2 is independent of PPARγ. The MEK/ERK inhibitor PD98059 dramatically repressed HtrA3 induction. Altogether, these data indicate that 15dPGJ2 is able to stimulate the expression of HtrA3 through an indirect mechanism involving the MEK/ERK pathway but independent of PPARγ. Our results provide a better understanding of the mechanisms involved in the regulation of HtrA3, a potential tumor suppressor gene. 相似文献
102.
目的:探讨renalase在人近曲肾小管上皮细胞系(HK-2)的表达与分泌,为进一步研究细胞水平renalase及其通路建立稳定的实验平台。方法:以HK-2细胞系作为研究材料。①应用Westernblot方法检测renalase蛋白的表达。②用real-timePCR方法检测renalasemRNA表达的变化。③用ELISA方法检测细胞上清液中renalase的浓度。结果:在mRNA水平及蛋白水平均检测到renalase表达。结论:首次在mRNA水平及蛋白水平证实了HK-2细胞能够表达renalase,为进一步研究儿茶酚胺或缺血缺氧刺激下细胞renalase的表达奠定了基础。 相似文献
103.
104.
Kiersztan A Lukasinska I Baranska A Lebiedzinska M Nagalski A Derlacz RA Bryla J 《Journal of inorganic biochemistry》2007,101(3):493-505
Although selenium is taken with diet mainly as selenoamino acids, its hypoglycaemic action on hepatic gluconeogenesis has been studied with the use of inorganic selenium derivatives. The aim of the present investigation was to compare relative efficacies of inorganic and organic selenium compounds in reducing glucose synthesis in hepatocytes and renal tubules, significantly contributing to the glucose homeostasis. In contrast to hepatocytes, both selenite and methylselenocysteine inhibited renal gluconeogenesis by about 40-45% in control rabbits. Selenate did not affect this process, whereas selenomethionine inhibited gluconeogenesis by about 20% in both hepatocytes and renal tubules. In contrast to methylselenocysteine, selenite decreased intracellular ATP content, glutathione reduced/glutathione oxidized (GSH/GSSG) ratio and pyruvate carboxylase, PEPCK and FBPase activities, while methylselenocysteine diminished PEPCK activity due to elevation of intracellular 2-oxoglutarate and GSSG, inhibitors of this enzyme. Experiments in vivo indicate that in 3 of 9 alloxan-diabetic rabbits treated for 14 days with methylselenocysteine (0.182mg/kg body weight) blood glucose level was normalized, whereas in all diabetic rabbits plasma creatinine and urea levels decreased from 2.52+/-0.18 and 87.4+/-9.7 down to 1.63+/-0.11 and 39.0+/-2.8, respectively. In view of these data selenium supplementation might be beneficial for protection against diabetes-induced nephrotoxicity despite selenium accumulation in kidneys and liver. 相似文献
105.
Wei SP Li XQ Chou CF Liang YY Peng JB Warnock DG Ma HP 《The Journal of membrane biology》2007,220(1-3):21-31
We used patch-clamp techniques and A6 distal nephron cells as a model to determine how cholesterol regulates the renal epithelial
sodium channel (ENaC). We found that luminal methyl-β-cyclodextrin (mβCD, a cholesterol scavenger) did not acutely affect
ENaC activity at a previously used concentration of 10 mm but significantly decreased ENaC activity both when the cell membrane was stretched and at a higher concentration of 50 mm. Luminal cholesterol had no effect on ENaC activity at a concentration of 50 μg/ml but significantly increased ENaC activity
both when the cell membrane was stretched and at a higher concentration of 200 μg/ml. Confocal microscopy data indicate that
membrane tension facilitates both mβCD extraction of cholesterol and A6 cell uptake of exogenous cholesterol. Together with
previous findings that cholesterol in the apical membrane is tightly packed with sphingolipids and that stretch can affect
lipid distribution, our data suggest that membrane tension modulates the effects of mβCD and cholesterol on ENaC activity,
probably by facilitating both extraction and enrichment of apical cholesterol. 相似文献
106.
Nadai M Kato M Yoshizumi H Kimura M Kurono S Abe F Saito H Hasegawa T 《Life sciences》2007,81(15):1175-1182
Whether organic anion and cation transporters are involved in the renal excretion of xanthine derivatives, 3-methylxanthie and enprofylline, remains unclear. In this study, we have investigated the effects of typically predominant substrates for organic anion and cation transporters on the tubular secretion of 3-methylxanthine and enprofylline in rats. In the renal clearance experiments using typical substrates for organic anion transporters, probenecid and p-aminohippurate, probenecid (20 mg/kg), but not p-aminohippurate (100 mg/kg), significantly decreased the renal clearance and clearance ratio of 3-methylxanthine and enprofylline. The typical substrates for organic cation transport systems, tetraethylammonium (30.6 mg/kg) and cimetidine (50 or 100 mg/kg), significantly decreased the renal clearance and clearance ratio of 3-methylxanthine and enprofylline. These results suggest that the renal secretory transport of 3-methylxanthine and enprofylline are mediated by probenecid-, cimetidine- and tetraethylammonium-sensitive transport systems. Uric acid, an organic anion, significantly inhibited the renal secretion of 3-methylxanthine, but not enprofylline, suggesting that the renal tubular transport of 3-methylxanthine is also mediated via uric acid-sensitive transport system. These findings suggest the possibility that both organic anion and cation transporters are, at least, involved in the renal tubular transport of 3-methylxanthine and enprofylline in rats. 相似文献
107.
Gao SY Li CY Shimokawa T Terashita T Matsuda S Yaoita E Kobayashi N 《Cell and tissue research》2007,328(2):391-400
Intercellular adhesions between renal glomerular epithelial cells (also called podocytes) are necessary for the proper function
of the glomerular filtration barrier. Although our knowledge of the molecular composition of podocyte cell-cell contact sites
has greatly progressed, the underlying molecular mechanism regulating the formation of these cell-cell contacts remains largely
unknown. We have used forskolin, an activator of adenylyl cyclase that elevates the level of intracellular cAMP, to investigate
the effect of cAMP and three Rho-family small GTPases (RhoA, Cdc42, and Rac1) on the regulation of cell-cell contact formation
in a murine podocyte cell line. Transmission electron microscopy and the immunostaining of cell adhesion molecules and actin-associated
proteins have revealed a structural change at the site of cell-cell contact following forskolin treatment. The activity of
the Rho-family small GTPases before and after forskolin treatment has been evaluated with a glutathione-S-transferase pull-down
assay. Forskolin reinforces the integrity of cell-cell contacts, resulting in the closure of an intercellular adhesion zipper,
accompanied by a redistribution of cell adhesion molecules and actin-associated proteins in a continuous linear pattern at
cell-cell contacts. The Rho-family small GTPases Rac1 and Cdc42 are activated during closure of the adhesion zipper, whereas
RhoA is suppressed. Thus, cAMP promotes the assembly of cell-cell contacts between podocytes via a mechanism that probably
involves Rho-family small GTPases.
This study was supported in part by a grant-in-aid for scientific research from the Japanese Ministry for Education, Culture,
Sports, Science, and Technology (to N. K., no. 14570015). S-Y.G. is a recipient of a grant awarded by the Japanese government
to graduate students from foreign countries. 相似文献
108.
Terada Y Inoshita S Kuwana H Kobayashi T Okado T Ichijo H Sasaki S 《Biochemical and biophysical research communications》2007,364(4):1043-1049
We investigated the role of apoptosis signal-regulating kinase 1 (ASK1) in ischemia/reperfusion (I/R)-induced acute kidney injury (AKI). Blood urea nitrogen (BUN) and serum creatinine were significantly higher in ASK1+/+ mice than in ASK1−/− mice after I/R injury. Renal histology of ASK1+/+ mice showed significantly greater tubular necrosis and degradation. In ASK1−/− mice, phosphorylation of ASK1, JNK, and p38K, and the number of TUNEL-positive cells and infiltrated leukocytes decreased after I/R injury. Apoptotic changes were significantly decreased in cultured renal tubular epithelial cells (TECs) from ASK1−/− mice under hypoxic condition. Transfection with dominant-active ASK1 induced apoptosis in TECs. Protein expression of monocyte chemoattractant protein-1 (MCP-1) was significantly weaker in ASK1−/− mice after I/R injury. Transfection with dominant negative-ASK1 significantly decreased MCP-1 production in TECs. These results demonstrated that ASK1 is activated in I/R-induced AKI, and blockage of ASK1 attenuates renal tubular apoptosis, MCP-1 expression, and renal function. 相似文献
109.
Leonhartsberger N Ramoner R Putz T Gander H Rahm A Falkensammer C Bartsch G Thurnher M 《Cancer immunology, immunotherapy : CII》2007,56(6):897-903
The ability of cultured, antigen-loaded dendritic cells (DCs) to induce antigen-specific T cell immunity in vivo has previously
been demonstrated and confirmed. Immune monitoring naturally focuses on immunity against vaccine antigens and may thus ignore
other effects of DC vaccination. Here we therefore focused on antigen-independent responses induced by DC vaccination of renal
cell carcinoma patients.
In addition to the anticipated response against the vaccine antigen KLH, vaccination with CD83+ monocyte-derived DCs resulted in a strong increase in the ex vivo proliferative and cytokine responses of PBMCs stimulated
with LPS or BCG. In addition, LPS strongly enhanced the KLH-induced proliferative and cytokine response of PBMCs. Moreover,
proliferative and cytokine responses of PBMCs stimulated with the homeostatic cytokines IL-7 and IL-15 were also clearly enhanced
after DC vaccination. In contrast to LPS induced proliferation, which is well known to depend on monocytes, IL-7 induced proliferation
was substantially enhanced after monocyte depletion indicating that monocytes limit IL-7 induced lymphocyte expansion.
Our data indicate that DC vaccination leads to an increase in the ex vivo responsiveness of patient PBMCs consistent with
a DC vaccination induced enhancement of T cell memory. Our findings also suggest that incorporation of bacterial components
and homeostatic cytokines into immunotherapy protocols may be useful in order to enhance the efficacy of DC vaccination and
that monocytes may limit DC vaccination induced immunity.
Supported by a grant to Martin Thurnher from the kompetenzzentrum medizin tirol (kmt), a center of excellence. 相似文献
110.
Søndergaard H Frederiksen KS Thygesen P Galsgaard ED Skak K Kristjansen PE Odum N Kragh M 《Cancer immunology, immunotherapy : CII》2007,56(9):1417-1428
Interleukin (IL)-21 is a recently discovered cytokine in early clinical development, which has shown anti-tumor activity in
various animal models. In the present study, we examine the anti-tumor activity of IL-21 protein therapy in two syngeneic
tumor models and its effect on the density of tumor infiltrating T cells. We treated mice bearing established subcutaneous
B16 melanomas or RenCa renal cell carcinomas with intraperitoneal (i.p.) or subcutaneous (s.c.) IL-21 protein therapy and
subsequently scored the densities of tumor infiltrating CD4+ and CD8+ T cells by immunohistochemistry. Whereas both routes of IL-21 administration significantly inhibited growth of small, established
RenCa and B16 tumors, only s.c. therapy significantly inhibited the growth of large, established tumors. We found a greater
bioavailability and significant drainage of IL-21 to regional lymph nodes following s.c. administration, which could account
for the apparent increase in anti-tumor activity. Specific depletion of CD8+ T cells with monoclonal antibodies completely abrogated the anti-tumor activity, whereas NK1.1+ cell depletion did not affect tumor growth. In accordance, both routes of IL-21 administration significantly increased the
density of tumor infiltrating CD8+ T cells in both B16 and RenCa tumors; and in the RenCa model s.c. administration of IL-21 led to a significantly higher density
of tumor infiltrating CD8+ T cells compared to i.p. administration. The densities of CD4+ T cells were unchanged following IL-21 treatments. Taken together, these data demonstrate that IL-21 protein has anti-tumor
activity in established syngeneic tumors, and we show that IL-21 therapy markedly increases the density of tumor infiltrating
CD8+ T cells. 相似文献