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Alexander R. Ball Jr. Yen-Yun ChenKyoko Yokomori 《Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms》2014,1839(3):191-202
Cohesins are conserved and essential Structural Maintenance of Chromosomes (SMC) protein-containing complexes that physically interact with chromatin and modulate higher-order chromatin organization. Cohesins mediate sister chromatid cohesion and cellular long-distance chromatin interactions affecting genome maintenance and gene expression. Discoveries of mutations in cohesin's subunits and its regulator proteins in human developmental disorders, so-called “cohesinopathies,” reveal crucial roles for cohesins in development and cellular growth and differentiation. In this review, we discuss the latest findings concerning cohesin's functions in higher-order chromatin architecture organization and gene regulation and new insight gained from studies of cohesinopathies. This article is part of a Special Issue entitled: Chromatin and epigenetic regulation of animal development. 相似文献
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Lucie Post Cécile Garnaud Danièle Maubon Hervé Pelloux Catherine Mansard Annick Bosseray Céline Dard 《Parasitology international》2018,67(1):1-3
Cystoisospora belli (previously known as Isospora belli) is a tropical coccidian parasite sometimes leading to severe diarrhea in immunocompromised patients. Here we describe a fatal case of cystoisosporiasis in a non HIV-immunocompromised 71-year-old female with no recent travel history. Infection was either latent or potentially caused by the consumption of contaminated imported food from Asia. Diagnosis was made by microscopical detection of numerous C. belli oocysts in stools without specific staining. Treatment with TMP-SMZ slightly improved diarrhea within 3 days, but dehydration subsequently led to acute decompensated heart failure and a fatal evolution. This report illustrates the possibility of severe cystoisosporiasis in non HIV-immunocompromised patients in a non-endemic country and highlights the risk of transmission through imported contaminated food consumption. 相似文献
35.
Bruno César Feltes Conrado Pedebos Diego Bonatto Hugo Verli 《Biochimica et Biophysica Acta (BBA)/General Subjects》2018,1862(12):2579-2589
Background
Xeroderma Pigmentosum (XP) is a disease caused by mutations in the nucleotide excision repair (NER) pathway. Patients with XP exhibit a high propensity to skin cancers and some subtypes of XP can even present neurological impairments. During NER, DDB2 (XPE), in complex with DDB1 (DDB-Complex), performs the DNA lesion recognition. However, not much is known about how mutations found in XP patients affect the DDB2 structure and complex assembly. Thus, we searched for structural evidence associated with the role of three naturally occurring mutations found in XPE patients: R273H, K244E, and L350P.Methods
Each mutant was individually constructed and submitted to multiple molecular dynamics simulations, done in triplicate for each designed system. Additionally, Dynamic Residue Interaction Networks were designed for each system and analyzed parallel with the simulations.Results
DDB2 mutations promoted loss of flexibility in the overall protein structure, producing a different conformational behavior in comparison to the WT, especially in the region comprising residues 354 to 371. Furthermore, the DDB-complex containing the mutated forms of DDB2 showed distinct behaviors for each mutant: R273H displayed higher structural instability when complexed; L350P affected DDB1 protein-protein binding with DDB2; and K244E, altered the complex binding trough different ways than L350P.Conclusions
The data gathered throughout the analyses helps to enlighten the structural basis for how naturally occurring mutations found in XPE patients impact on DDB2 and DDB1 function.General significance
Our data influence not only on the knowledge of XP but on the DNA repair mechanisms of NER itself. 相似文献36.
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A number of viral gene products are capable of triggering apoptotic cell death through interfering with cellular signaling cascades, including the Akt kinase pathway. In this study, the pro-apoptotic role of the SARS-CoV Membrane (M) structural protein is described. We found that the SARS-CoV M protein induced apoptosis in both HEK293T cells and transgenic Drosophila. We further showed that M protein-induced apoptosis involved mitochondrial release of cytochrome c protein, and could be suppressed by caspase inhibitors. Over-expression of M caused a dominant rough-eye phenotype in adult Drosophila. By performing a forward genetic modifier screen, we identified phosphoinositide-dependent kinase-1 (PDK-1) as a dominant suppressor of M-induced apoptotic cell death. Both PDK-1 and Akt kinases play essential roles in the cell survival signaling pathway. Altogether, our data show that SARS-CoV M protein induces apoptosis through the modulation of the cellular Akt pro-survival pathway and mitochondrial cytochrome c release. 相似文献
38.
Barr J Sharma CS Sarkar S Wise K Dong L Periyakaruppan A Ramesh GT 《Molecular and cellular biochemistry》2007,304(1-2):93-99
Super CitriMax (HCA-SX) is a novel calcium/potassium salt of (−)-hydroxycitric acid extracted from the dried fruit rind of
the plant Garcinia cambogia, and commonly consumed as weight loss dietary supplement. In the present study, we investigated the effect of HCA-SX on inflammation,
oxidative stress and insulin resistance in developing obese Zucker rats, an animal model of type II diabetes associated with
inflammation and oxidative stress. Male Zucker rats (5-week old) were supplemented with vehicle (control) and HCA-SX in drinking
water for 7 weeks. Oxidative stress markers, including malondialdehyde (MDA), protein carbonyl (DNPH), and protein tyrosine
nitration (tyr-NO2) were measured in the liver and kidney tissues using biochemical and immunoblotting techniques. Compared to controls, the
levels of MDA, DNPH and tyr-NO2 were lower in the liver and kidney of HCA-SX-treated animals. Furthermore, the levels of C-reactive protein and interleukin-6,
markers of inflammation measured by ELISA, were lower in the plasma of HCA-SX-supplemented animals compared to controls, as
were levels of fasting plasma insulin, glucose, and triglycerides. Interestingly, insulin resistance did not develop in HCA-SX-supplemented
rats. Food-intake and body weight gain was also lower in rats supplemented with HCA-SX compared to their control counterparts.
These results suggest that HCA-SX supplementation in obese Zucker rats reduces food-intake, body weight gain, and also attenuates
the increases in inflammation, oxidative stress, and insulin resistance observed in untreated animals. Therefore, HCA-SX may
be used as an intervention to overcome obesity-related complications, including inflammation, oxidative stress, and insulin
resistance. 相似文献
39.
The androgen theory of autism proposes that autism spectrum conditions (ASC) are in part due to elevated fetal testosterone (FT) levels, which are positively correlated with a number of autistic traits and inversely correlated with social development and empathy. A medical questionnaire was completed by n=54 women with ASC, n=74 mothers of children with ASC, and n=183 mothers of typically developing children to test whether women with ASC have an increased rate of testosterone-related medical conditions, and to see whether mothers of children with ASC show similar abnormalities, as part of the 'broader autism phenotype'. Compared to controls, significantly more women with ASC reported (a) hirsutism, (b) bisexuality or asexuality, (c) irregular menstrual cycle, (d) dysmenorrhea, (e) polycystic ovary syndrome, (f) severe acne, (g) epilepsy, (h) tomboyism, and (i) family history of ovarian, uterine, and prostate cancers, tumors, or growths. Compared to controls, significantly more mothers of ASC children reported (a) severe acne, (b) breast and uterine cancers, tumors, or growths, and (c) family history of ovarian and uterine cancers, tumors, or growths. These results suggest current hormone abnormalities in women with ASC and their mothers. Direct investigations of serum testosterone levels and genetic susceptibility to high testosterone production or sensitivity in women with ASC would illuminate the origin of these conditions. The relationship between FT and current testosterone levels also needs to be clarified. The present results may be relevant to understanding the increased male risk to developing autism. 相似文献
40.
Maintenance of the shape of biological tubules is critical for development and physiology of metazoan organisms. Loss of function of the Caenorhabditis elegans FGD protein EXC-5 allows large fluid-filled cysts to form in the lumen of the single-cell excretory canal tubules, while overexpression of exc-5 causes defects at the tubule's basolateral surface. We have examined the effects of altering expression levels of exc-5 on the distribution of fluorescently-marked subcellular organelles. In exc-5 mutants, early endosomes build up in the cell, especially in areas close to cysts, while recycling endosomes are depleted. Endosome morphology changes prior to cyst formation. Conversely, when exc-5 is overexpressed, recycling endosomes are enriched. Since FGD proteins activate the small GTPases CDC42 and Rac, these results support the hypothesis that EXC-5 acts through small GTPases to move material from apical early endosomes to recycling endosomes, and that loss of such movement is likely the cause of tubule deformation both in nematodes and in tissues affected by FGD dysfunction such as Charcot–Marie–Tooth Syndrome type 4H. 相似文献