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排序方式: 共有419条查询结果,搜索用时 23 毫秒
61.
Marina Mikhaylova Julia Bär Bas van Bommel Philipp Schätzle PingAn YuanXiang Rajeev Raman Johannes Hradsky Anja Konietzny Egor Y. Loktionov Pasham Parameshwar Reddy Jeffrey Lopez-Rojas Christina Spilker Oliver Kobler Syed Ahsan Raza Oliver Stork Casper C. Hoogenraad Michael R. Kreutz 《Neuron》2018,97(5):1110-1125.e14
62.
Humans have been exposed to many environmental challenges since their evolutionary origins in Africa and subsequent migrations to the rest of the world. A severe environmental challenge to human migrants was hypoxia caused by low barometric oxygen pressure at high altitudes. Several genome-wide scans have elucidated the genetic basis of human high-altitude adaptations.However, the dearth of functional variant information has led to the successful association of only a few candidate genes. In the present study, we employed a candidate gene approach and re-sequenced the EDAR locus in 45 Tibetan individuals to identify mutations involved in hypoxia adaptation. We identified 10 and five quantitative trait-associated mutations for oxygen saturation (SaO_2) and blood platelet count, respectively, at the EDAR locus. Among these, rs10865026 and rs3749110 (associated with SaO_2 and platelet count, respectively) were identified as functional candidate targets. These data demonstrate that EDAR has undergone natural selection in recent human history and indicate an important role of EDAR variants in Tibetan high-altitude adaptations. 相似文献
63.
Pál Stráner Eszter Balogh Gusztáv Schay Christelle Arrondel ágnes Mikó Gerda LAuné Alexandre Benmerah András Perczel Dóra K. Menyhárd Corinne Antignac Géraldine Mollet Kálmán Tory 《生物化学与生物物理学报:疾病的分子基础》2018,1864(7):2448-2457
Interallelic interactions of membrane proteins are not taken into account while evaluating the pathogenicity of sequence variants in autosomal recessive disorders. Podocin, a membrane-anchored component of the slit diaphragm, is encoded by NPHS2, the major gene mutated in hereditary podocytopathies. We formerly showed that its R229Q variant is only pathogenic when trans-associated to specific 3′ mutations and suggested the causal role of an abnormal C-terminal dimerization. Here we show by FRET analysis and size exclusion chromatography that podocin oligomerization occurs exclusively through the C-terminal tail (residues 283–382): principally through the first C-terminal helical region (H1, 283–313), which forms a coiled coil as shown by circular dichroism spectroscopy, and through the 332–348 region. We show the principal role of the oligomerization sites in mediating interallelic interactions: while the monomer-forming R286Tfs*17 podocin remains membranous irrespective of the coexpressed podocin variant identity, podocin variants with an intact H1 significantly influence each other's localization (r2?=?0.68, P?=?9.2?×?10?32). The dominant negative effect resulting in intracellular retention of the pathogenic F344Lfs*4-R229Q heterooligomer occurs in parallel with a reduction in the FRET efficiency, suggesting the causal role of a conformational rearrangement. On the other hand, oligomerization can also promote the membrane localization: it can prevent the endocytosis of F344Lfs*4 or F344* podocin mutants induced by C-terminal truncation. In conclusion, C-terminal oligomerization of podocin can mediate both a dominant negative effect and interallelic complementation. Interallelic interactions of NPHS2 are not restricted to the R229Q variant and have to be considered in compound heterozygous individuals. 相似文献
64.
65.
Sayed H. Raza Habib R. Athar Muhammad Ashraf Amjad Hameed 《Environmental and Experimental Botany》2007,60(3):368-376
Modulation of water relations, activities of antioxidant enzymes and ion accumulation was assessed in the plants of two wheat cultivars S-24 (salt tolerant) and MH-97 (moderately salt sensitive) subjected to saline conditions and glycinebetaine (GB) applied foliarly. Different levels of GB, i.e., 0 (unsprayed), 50 and 100 mM (in 0.10% Tween-20 solution) were applied to the wheat plants at the vegetative growth stage. Leaf water potential, leaf osmotic potential and turgor potential were decreased due to salt stress. Salt stress increased the Na+ and Cl− accumulation coupled with a decrease in K+ and Ca2+ in the leaves and roots of both cultivars thereby decreasing tissue K+/Na+ and Ca2+/Na+ ratios. Furthermore, salt stress decreased the activities of superoxide dismutase (SOD), whereas it increased the activities of catalase (CAT) and peroxidase (POD) in both wheat cultivars. However, accumulation of GB in the leaves of both wheat cultivars was consistently increased with an increase in concentration of exogenous GB application under both non-saline and saline conditions. Accumulation of Na+ was decreased with an increase in K+ accumulation upon a consistent increase in GB accumulation under salt stress conditions thereby resulting in better K+/Na+ and Ca2+/Na+ ratios in the leaves and roots. High accumulation of GB and K+ mainly contributed to osmotic adjustment, which is one of the factors known to be responsible for improving growth and yield under salt stress. The activities of all antioxidant enzymes, SOD, CAT and POD were enhanced by GB application in cv. MH-97 under saline conditions, whereas all these except SOD were reduced in cv. S-24. It is likely that both applied GB and intrinsic SOD scavenged ROS in the tolerant cultivar thereby resulting into low activities of CAT and POD enzymes under salt stress. In conclusion, the adverse effects of salt stress on wheat can be alleviated by the exogenous application of 100 mM GB by modulating activities of antioxidant enzymes and changes in water relations and ion homeostasis. Furthermore, effectiveness of GB application on regulation of activities of antioxidant enzymes was found to be cultivar-specific. 相似文献
66.
Batur Avgan Hana Raza Muhammadsaddik Barzani Urs Breitenmoser 《Zoology in the Middle East.》2016,62(2):95-104
The status of leopard in Iraq and south-eastern Turkey has been unclear for decades. Because of recent and on-going armed conflicts in important parts of the potential leopard distribution range, no studies were done that could have proved the presence of the species. We report here 10 confirmed and 2 unconfirmed leopard records between 2001 and 2014 from northern Iraq and south-eastern Turkey. All records for which the gender of the animal was identified were of males, which could be hypothesized as long-range dispersers from Iran. However, the long distances between our records and the nearest known breeding populations in Iran suggests that a so far unnoticed reproducing population nuclei may occur along the north-western part of the Zagros Mountains in western Iran, northern Iraq and south-eastern Turkey. 相似文献
67.
S W Davies M Turmaine B A Cozens A S Raza A Mahal L Mangiarini G P Bates 《Philosophical transactions of the Royal Society of London. Series B, Biological sciences》1999,354(1386):981-989
Huntington's disease (HD) is an inherited progressive neurodegenerative disease caused by the expansion of a polyglutamine repeat sequence within a novel protein. Recent work has shown that abnormal intranuclear inclusions of aggregated mutant protein within neurons is a characteristic feature shared by HD and several other diseases involving glutamine repeat expansion. This suggests that in each of the these disorders the affected nerve cells degenerate as a result of these abnormal inclusions. A transgenic mouse model of HD has been generated by introducing exon 1 of the HD gene containing a highly expanded CAG sequence into the mouse germline. These mice develop widespread neuronal intranuclear inclusions and neurodegeneration specifically within those areas of the brain known to degenerate in HD. We have investigated the sequence of pathological changes that occur after the formation of nuclear inclusions and that precede neuronal cell death in these cells. Although the relation between inclusion formation and neurodegeneration has recently been questioned, a full characterization of the pathways linking protein aggregation and cell death will resolve some of these controversies and will additionally provide new targets for potential therapies. 相似文献
68.
69.
Aun Raza Shumaila Bano Xiuquan Xu Rong Xian Zhang Haider Khalid Furqan Muhammad Iqbal Changkun Xia Jian Tang Zhen Ouyang 《Biological trace element research》2017,178(1):160-169
The rutin–nickel (II) complex (RN) was synthesized and characterized by elemental analysis, UV–visible spectroscopy, IR, mass spectrometry, 1H NMR, TG-DSC, SEM, and molar conductivity. The low molar conductivity value investigates the non-electrolyte nature of the complex. The elemental analysis and other physical and spectroscopic methods reveal the 1:2 stoichiometric ratio (metal/ligand) of the complex. An antioxidant study of rutin and its metal complex against DPPH radical showed that the complex has more radical scavenging activity than free rutin. The interaction of complex RN with DNA was determined using fluorescence spectra and agarose gel electrophoresis. The results showed that RN can intercalate moderately with DNA, quench a strong intercalator ethidium bromide (EB), and compete for the intercalative binding sites. The complex showed significant cleavage of pBR 322 DNA from supercoiled form (SC) to nicked circular form (NC), and these cleavage effects were dose-dependent. Moreover, the mechanism of DNA cleavage indicated that it was a hydrolytic cleavage pathway. These results revealed the potential nuclease activity of the complex to cleave DNA. 相似文献
70.
Naqvi RA Hussain A Raish M Noor A Shahid M Sarin R Kukreti H Khan NJ Ahmad S Deo SV Husain SA Pasha ST Basir SF Shukla NK 《DNA and cell biology》2008,27(9):517-525
Even after tremendous molecular studies, early detection,more accurate and sensitive diagnosis, and prognosis of breast cancer appear to be a riddle so far. To stab the enigma, this study is designed to envisage DNA methylation signatures as cancer-specific and stage-specific biomarkers in Indian patients. Rigorous review of scattered scientific reports on aberrant DNA methylation helped us to select and analyze a potential tumor suppressor gene pair (FHIT and p16 genes) in breast cancer patients. Methylation signatures from 232 primary sporadic breast cancer patients were pinpointed by methylation-specific PCR (MSP). To increase the sensitivity, we combined both MSP and expression studies (RT-PCR and Northern blotting) in a reproducible manner. Statistical analysis illustrated that hypermethylation of FHIT gene ( p < 0.0001) and p16 gene ( p=0.04) may be used as a potential diagnostic marker to diagnose the early and locally advanced stages of breast cancer. Additionally, the study authenticates the dependency of methylation and expressional loss of p16 gene on FHIT gene silencing. This observation not only describes the severity of disease when both genes are silenced but also drives to speculate the molecular cross talk between two genes or genetic pathways dictated by them separately. 相似文献