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1.
Mitochondrial dynamics play a critical role in deciding the fate of a cell under normal and diseased condition. Recent surge of studies indicate their regulatory role in meeting energy demands in renal cells making them critical entities in the progression of diabetic nephropathy. Diabetes is remarkably associated with abnormal fuel metabolism, a basis for free radical generation, which if left unchecked may devastate the mitochondria structurally and functionally. Impaired mitochondrial function and their aberrant accumulation have been known to be involved in the manifestation of diabetic nephropathy, indicating perturbed balance of mitochondrial dynamics, and mitochondrial turnover. Mitochondrial dynamics emphasize the critical role of mitochondrial fission proteins such as mitochondrial fission 1, dynamin-related protein 1 and mitochondrial fission factor and fusion proteins including mitofusin-1, mitofusin-2 and optic atrophy 1. Clearance of dysfunctional mitochondria is aided by translocation of autophagy machinery to the impaired mitochondria and subsequent activation of mitophagy regulating proteins PTEN-induced putative kinase 1 and Parkin, for which mitochondrial fission is a prior event. In this review, we discuss recent progression in our understanding of the molecular mechanisms targeting reactive oxygen species mediated alterations in mitochondrial energetics, mitophagy related disorders, impaired glucose transport, tubular atrophy, and renal cell death. The molecular cross talks linking autophagy and renoprotection through an intervention of 5′-AMP-activated protein kinase, mammalian target of rapamycin, and SIRT1 factors are also highlighted here, as in-depth exploration of these pathways may help in deriving therapeutic strategies for managing diabetes provoked end-stage renal disease. 相似文献
2.
Jiaohong Zhao Fudan Gao Jingsong Zhang Teruo Ogawa Weimin Ma 《The Journal of biological chemistry》2014,289(39):26669-26676
Two mutants that grew faster than the wild-type (WT) strain under high light conditions were isolated from Synechocystis sp. strain PCC 6803 transformed with a transposon-bearing library. Both mutants had a tag in ssl1690 encoding NdhO. Deletion of ndhO increased the activity of NADPH dehydrogenase (NDH-1)-dependent cyclic electron transport around photosystem I (NDH-CET), while overexpression decreased the activity. Although deletion and overexpression of ndhO did not have significant effects on the amount of other subunits such as NdhH, NdhI, NdhK, and NdhM in the cells, the amount of these subunits in the medium size NDH-1 (NDH-1M) complex was higher in the ndhO-deletion mutant and much lower in the overexpression strain than in the WT. NdhO strongly interacts with NdhI and NdhK but not with other subunits. NdhI interacts with NdhK and the interaction was blocked by NdhO. The blocking may destabilize the NDH-1M complex and repress the NDH-CET activity. When cells were transferred from growth light to high light, the amounts of NdhI and NdhK increased without significant change in the amount of NdhO, thus decreasing the relative amount of NdhO. This might have decreased the blocking, thereby stabilizing the NDH-1M complex and increasing the NDH-CET activity under high light conditions. 相似文献
3.
目的:探究骨化三醇联合补气口服液对慢性肾功能衰竭患者血清瘦素及睾酮水平的影响。方法:选取我院诊治慢性肾功能衰竭患者116例为研究对象,根据随机数字对照表分为对照组(58例)与试验组(58例)。两组患者均常规给予血管紧张素酶抑制剂或β受体阻滞剂,对照组给予口服骨化三醇胶丸,试验组在对照组的基础上联合给予补气口服液。治疗结束后,比较两组患者肾功能指标、血清瘦素及睾酮水平、营养生化指标。结果:治疗结束后,两组患者血清肌酐(Cr)、血尿素氮(BUN)及瘦素水平均较治疗前显著降低(P0.05),睾酮、血钙水平较治疗前升高(P0.05),血磷水平降低(P0.05)。与对照组相比,试验组血Cr、BUN及瘦素水平较低(P0.05),而血清睾酮、血钙水平较高,血磷水平较低(P0.05)。结论:骨化三醇联合补气口服液能够更有效改善慢性肾功能衰竭患者的肾功能,纠正患者体内电解质紊乱,改善患者食欲不振营养不良症状,推测其与降低血清瘦素水平及升高睾酮水平有关。 相似文献
4.
Autophagy is involved in mouse kidney development and podocyte differentiation regulated by Notch signalling 下载免费PDF全文
《Journal of cellular and molecular medicine》2017,21(7):1315-1328
Podocyte dysfunction results in glomerular diseases accounted for 90% of end‐stage kidney disease. The evolutionarily conserved Notch signalling makes a crucial contribution in podocyte development and function. However, the underlying mechanism of Notch pathway modulating podocyte differentiation remains less obvious. Autophagy, reported to be related with Notch signalling pathways in different animal models, is regarded as a possible participant during podocyte differentiation. Here, we found the dynamic changes of Notch1 were coincided with autophagy: they both increased during kidney development and podocyte differentiation. Intriguingly, when Notch signalling was down‐regulated by DAPT, autophagy was greatly diminished, and differentiation was also impaired. Further, to better understand the relationship between Notch signalling and autophagy in podocyte differentiation, rapamycin was added to enhance autophagy levels in DAPT‐treated cells, and as a result, nephrin was recovered and DAPT‐induced injury was ameliorated. Therefore, we put forward that autophagy is involved in kidney development and podocyte differentiation regulated by Notch signalling. 相似文献
5.
《Saudi Journal of Biological Sciences》2019,26(8):1982-1985
ObjectiveTo elaborate the significance of combined detection of cystatin C, urinary micro-albumin (mAlb) and β2-microglobulin (β2-MG) in diagnosis of the early renal injury in pregnancy-induced hypertension syndrome.MethodsA total of 120 patients with pregnancy-induced hypertension syndrome who were admitted to this hospital for treatment between November 2015 and October 2018 were enrolled as subjects, and divided into the control group (without complication of renal injury, n = 76) and the observation group (with complication of renal injury, n = 44) according to the complications of early renal injury. Furthermore, 60 patients who participated in the antenatal care in this hospital were enrolled as the normal subjects (normal group). Automatic biochemistry analyzer was utilized to measure CysC, urinary mAlb and β2-MG in serum to evaluate the specificity, sensitivity, accuracy, positive predictive value (PPV) and negative predictive value (NPV) of single or combined measurements of these indexes in diagnosis of the early renal injury in pregnancy-induced hypertension syndrome.ResultsIn the observation group, the levels of CysC, urinary mAlb and β2-MG were higher than those in the control group, while the levels in the normal group were the lowest (P < 0.05). Combined measurement of CysC, urinary mAlb and β2-MG showed a higher accuracy (90.0%) in diagnosis of the early renal injury in pregnancy-induced hypertension syndrome than the single measurements, and the difference had statistical significance (P < 0.05). Besides, the sensitivity, specificity, PPV and NPV of the combined measurements were 94.59%, 87.30%, 81.40% and 94.49%, slightly higher than the single measurements, with no statistical significance in differences (P > 0.05).ConclusionCysC, urinary mAlb and β2-MG can reflect the renal injury effectively, and the combined measurements shows potent accuracy in diagnosis of the early renal injury in pregnancy-induced hypertension syndrome, thereby providing the scientific evidence for early diagnosis and stipulation of rational therapeutic regimen and improving the pregnancy outcome. 相似文献
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8.
李红艳 《中国实验动物学报》2008,16(1):59-61
目的比较大鼠肾大部切除与肾结扎两种方法制备的5/6肾切除慢性肾功能不全模型的异同。方法雄性SD大鼠随机分为三组。A组行左肾2/3切除加右肾切除,B组行结扎左肾动脉2/3分支加右肾切除,C组为假手术组。分别于第二次手术后5周、9周及13周测血压,处死大鼠,留取24h尿及肾组织。检测尿蛋白,肾组织切片染色。用半定量法评价肾小球硬化指数。结果第5周时,B组大鼠的收缩压显著升高,而A组与C组相比无显著差异,第9周和13周A组和B组与C组大鼠相比,收缩压均显著升高。肾部分切除术后,尿蛋白随时间进行性增加。B组与A组相比,尿蛋白增加更为显著。A组和B组在各观察点均有不同程度肾小球硬化,B组较A组肾小球硬化程度重。结论肾大部切除和肾结扎两种方法制备的大鼠5/6肾切除模型表现有所不同。 相似文献
9.
Tzong-Yuan Lin Tobias Werther Jae-Hun Jeoung Holger Dobbek 《The Journal of biological chemistry》2012,287(45):38338-38346
The three-component toluene dioxygenase system consists of an FAD-containing reductase, a Rieske-type [2Fe-2S] ferredoxin, and a Rieske-type dioxygenase. The task of the FAD-containing reductase is to shuttle electrons from NADH to the ferredoxin, a reaction the enzyme has to catalyze in the presence of dioxygen. We investigated the kinetics of the reductase in the reductive and oxidative half-reaction and detected a stable charge transfer complex between the reduced reductase and NAD+ at the end of the reductive half-reaction, which is substantially less reactive toward dioxygen than the reduced reductase in the absence of NAD+. A plausible reason for the low reactivity toward dioxygen is revealed by the crystal structure of the complex between NAD+ and reduced reductase, which shows that the nicotinamide ring and the protein matrix shield the reactive C4a position of the isoalloxazine ring and force the tricycle into an atypical planar conformation, both factors disfavoring the reaction of the reduced flavin with dioxygen. A rapid electron transfer from the charge transfer complex to electron acceptors further reduces the risk of unwanted side reactions, and the crystal structure of a complex between the reductase and its cognate ferredoxin shows a short distance between the electron-donating and -accepting cofactors. Attraction between the two proteins is likely mediated by opposite charges at one large patch of the complex interface. The stability, specificity, and reactivity of the observed charge transfer and electron transfer complexes are thought to prevent the reaction of reductaseTOL with dioxygen and thus present a solution toward conflicting requirements. 相似文献
10.
Paul R. Goodyer Gerald Lancaster Marie Villeneuve Charles R. Scriver 《Biochimica et Biophysica Acta (BBA)/General Subjects》1980,633(2):191-200
Mitochondrial 4-aminobutyrate aminotransferase in rat kidney can utilize pyruvate as the acceptor for the amino group of 4-aminobutyrate. Renal 4-aminobutyrate aminotransferase activity at saturating equimolar concentration of 4-aminobutyrate and 5 mM pyruvate is 42.8 ± 2.5 μmol/g protein per h (mean ± S.E.M.) or 70% of 4-aminobutyrate aminotransferase activity with equimolar α-ketoglutarate. 4-Aminobutyrate aminotransferase in brain does not transaminate with pyruvate. Since pyruvate is an important mitochondrial metabolite in kidney, net disposal of glutamate via the 4-aminobutyrate pathway is possible. The renal 4-aminobutyrate pathway in the rat has other distinctive features when compared with the pathway in rat brain. Most inhibitors of rat neuronal glutamate decarboxylase were ineffective against the renal form of the enzyme, but 20 mM semicarbazide inhibited the latter form by 80% (P < 0.001) in vitro and reduced renal 4-aminobutyrate content by 75% (P < 0.001) in vivo. In the presence of 20 mM semicarbazide, ammoniagenesis by rat renal cortex slices incubated in 1 mM glutamine was inhibited 26% (P < 0.01). Semicarbazide was proportionately less effective (15% inhibition) when ammoniagenesis was stimulated (+243%) in slices prepared from chronically acidotic animals, and was no deterrant to ammoniagenesis when non-acidotic slices were incubated in supraphysiologic concentrations of 10 mM glutamine. We conclude that whereas integrity of the renal 4-aminobutyrate pathway may contribute to glutamate disposal and thus ammoniagenesis under physiologic conditions, the pathway is a passive participant in the overall process of ammoniagenesis. 相似文献