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排序方式: 共有129条查询结果,搜索用时 31 毫秒
31.
Khurshid I. Molvi Vasudevan Sudarsanam Madhubhai M. Patel Navedul Haque 《Journal of enzyme inhibition and medicinal chemistry》2013,28(6):819-828
A new series of tetrasubstituted thiophene analogues (4a-4f, 5a-5f and 8a-8i) were designed incorporating the pharmacophoric features of COX-1 (as in fenamates), 5-LOX and the p38 MAP kinase inhibitors. The designed series was synthesized by nucleophilic addition of aryl/aroylisothiocyanate and enamine (2) yielding the addition product l-(α-Carbomethoxy-β-aminothiocrotonoyl)-aryl/aroyl amines (3/7); which on reaction with substituted phenacyl bromides gave the targeted tetrasubstituted thiophene esters (4a-4f / 8a-8i). The tetrasubstituted thiophenes esters (4a-4f ) on hydrolysis with one equivalent of potassium hydroxide solution in methanol at room temperature gave corresponding acids (5a-5f ). All the targeted compounds were evaluated for their anti-inflammatory activity in carrageenin-induced rat hind paw oedema model at the doses of 10, 20 and 40 mg/kg body weight using standard drugs mefanamic acid and ibuprofen. The compounds (4c, 4e, 4f, 5f, 8a- 8i) which gave reasonable protection to the inflamed paw, eliciting good or moderate comparable anti-inflammatory activity were selected for investigating their analgesic activity using acetic acid induced writhing response test in albino mice at 10 mg/kg dose using standard drug ibuprofen and in order to arrive at possible mechanism of their anti-inflammatory activity, in vitro antioxidant nitric oxide radical scavenging assay at the concentrations of 5, 10, 15, 20, 25, 30 and 35 μg/mL were performed using standard drug ascorbic acid. 相似文献
32.
Muhammad Masroor Alam Adnan Khurshid Shahzad Shaukat Rana Muhammad Suleman Salmaan Sharif Mehar Angez Salman Akbar Malik Tahir Masood Ahmed Uzma Bashir Aamir Muhammad Naeem Syed Sohail Zahoor Zaidi 《PloS one》2013,8(6)
Pakistan harbors high disease burden of gastro-enteric infections with majority of these caused by rotavirus. Unfortunately, lack of proper surveillance programs and laboratory facilities have resulted in scarcity of available data on rotavirus associated disease burden and epidemiological information in the country. We investigated 1306 stool samples collected over two years (2008–2009) from hospitalized children under 5 years of age for the presence of rotavirus strains and its genotypic diversity in Lahore. The prevalence rate during 2008 and 2009 was found to be 34% (n = 447 out of 1306). No significant difference was found between different age groups positive for rotavirus (p>0.05). A subset of EIA positive samples was further screened for rotavirus RNA through RT-PCR and 44 (49.43%) samples, out of total 89 EIA positive samples, were found positive. G and P type prevalence was found as follows: G1P [4] = 3(6.81%); G1P [6] = 9(20.45%); G1P [8] = 1(2.27%); G2P [4] = 21(47.72%); G2P [8] = 1(2.27%); G9P [4] = 1(2.27%); G9P [6] = 1(2.27%) and G9P [8] = 7(15.90%). Phylogenetic analysis revealed that the VP7 and VP4 sequences clustered closely with the previously detected strains in the country as well as Belgian rotaviruses. Antigenic characterization was performed by analyzing major epitopes in the immunodominant VP7 and VP4 gene segments. Although the neutralization conferring motifs were found variable between the Pakistani strains and the two recommended vaccines strains (Rotarix™ and RotaTeq™), we validate the use of rotavirus vaccine in Pakistan based on the proven and recognized vaccine efficacy across the globe. Our findings constitute the first report on rotavirus’ genotype diversity, their phylogenetic relatedness and epidemiology during the pre-vaccination era in Lahore, Pakistan and support the immediate introduction of rotavirus vaccine in the routine immunization program of the country. 相似文献
33.
Muhammad Masroor Alam Adnan Khurshid Muhammad Suleman Rana Shahzad Shaukat Salmaan Sharif Mehar Angez Muhammad Naeem Syed Sohail Zahoor Zaidi 《PloS one》2013,8(4)
Astroviruses are globally known enteropathogens causing gastroenteritis and diarrhea, with eight well defined serotypes. Epidemiological studies have recognized serotype-1 as the most common subtype but no such data is available in Pakistan. During 2009–2010, we found astroviruses in 41 out of 535 (7%) samples collected from hospitalized children. Thirty one strains belonged to serotype-1 and clustered into two distinct lineages. Serotype-3, -4 and -6 were detected with 97–98% genetic homology to Indian and Chinese strains. 相似文献
34.
Shahzad Shaukat Mehar Angez Muhammad Masroor Alam Salmaan Sharif Adnan Khurshid Tariq Mahmood Syed Sohail Zahoor Zaidi 《PloS one》2013,8(11)
Non-polio enteroviruses (NPEVs) are among the most common viruses infecting humans worldwide. Most of these infections are asymptomatic but few can lead to systemic and neurological disorders like Acute Flaccid Paralysis (AFP). Acute Flaccid Paralysis is a clinical syndrome and NPEVs have been isolated frequently from the patients suffering from AFP but little is known about their causal relationship. The objective of this study was to identify and characterize the NPEV serotypes recovered from 184 stool samples collected from AFP patients in Federally Administered Tribal Areas (FATA) in north-west of Pakistan. Overall, 44 (95.6 %) isolates were successfully typed through microneutralization assay as a member of enterovirus B species including echovirus (E)-2, E-3, E-4, E-6, E-7, E-11, E-13, E-14, E-21 and E-29 while two isolates (PAK NIH SP6545B and PAK NIH SP1202B) remained untypeable. The VP1 and capsid regions analysis characterized these viruses as EV-B93 and EV-B106. Phylogenetic analysis confirmed that PAK NIH isolates had high genetic diversity and represent distinct genotypes circulating in the country. Our findings highlight the role of NPEVs in AFP cases to be thoroughly investigated especially in high disease risk areas, with limited surveillance activities and health resources. 相似文献
35.
Rukhshan Khurshid Mahjabeen Saleem Muhammad Saleem Akhtar Asmat Salim 《Molecular biology reports》2011,38(5):2953-2960
Granzymes kill cells in a variety of ways. They induce mitochondrial dysfunction through caspase dependent and caspase-independent
pathways and destroy DNA and the integrity of the nucleus. For gaining a better understanding of the molecular function of
granzyme M and its NK cell specificity, structural characterization of this enzyme by molecular modeling as well as its detailed
comparison with other granzymes is presented in this study. The study includes mode of action of granzyme M using cationic
binding sites, substrate specificity, post-translational structural modification and its functional relationship and interaction
of the enzyme with inhibitor in an attempt to explore how the activity of human granzyme M is controlled under physiological
conditions. It is concluded from the present study that the post-translational modification, including Oglycosylation of serine,
phosphorylation of serine and threonine and myristoylation of glycine, play an important role in the interaction of enzyme
with the cell surface membrane and regulate protein trafficking and stability. Phosphorylated serine and threonine also plays
a role in tumor elimination, viral clearance and tissue repair. In Gzm M there are cationic sites, cs1 and cs2 that may participate
in binding of Gzm M to the cell surface, thereby promoting its uptake and eventual release into the cytoplasm. Gzm M shows
apoptotic activity both by caspase dependent and independent pathways. Modeling of inhibitors bound to the granzyme active
site shows that the dimer also contributes to substrate specificity in a unique manner by extending the active-site cleft. 相似文献
36.
Khurshid Ahmad Saif Khan Mohd Adil Mohd Saeed Ashwini Kumar Srivastava 《Bioinformation》2014,10(4):191-195
Neurodegenerative disorders are often associated with excessive neuronal apoptosis. It is well known that apoptosis is regulated
by some intracellular proteases, such as, Caspases (cysteine-dependent, aspartate-specific proteases). In fact, Caspase-8 which is an
initiator caspase, has been identified as a key mediator of neuronal apoptosis. In addition, Caspase-8 is found to be coupled with
the regulation of various neurodegenerative disorders including Alzheimer׳s disease (AD), Parkinson׳s disease (PD), Huntington׳s
Diseases (HD) and Dentatorubral Pallidoluysian Atrophy (DRPLA). Caspase-8 inhibition may provide an effective means of
treatment for multiple neurodegenerative disorders. Therefore, the present study describes the molecular interaction of some
selected natural compounds with known anti neurodegenerative properties with Caspase-8. Docking between Caspase-8 and each
of these compounds (separately) was performed using ‘Autodock4.2’. Out of all the selected compounds, rosmarinic acid and
curcumin proved to be the most potent inhibitors of Caspase-8 with binding energy (ΔG) of -7.10 Kcal/mol and -7.08 Kcal/mol,
respectively. However, further in vitro and in vivo studies are needed to validate the anti-neurodegenerative potential of these
compounds. 相似文献
37.
Mushtaq A Beigh Mehvish Showkat Mahboob ul Hussain Shafat A Latoo Sheikh T Majeed Khurshid I Andrabi 《Cell communication and signaling : CCS》2012,10(1):1-5
Background
Ribosomal protein S6 kinase 1(S6K1) is an evolutionary conserved kinase that is activated in response to growth factors and viral stimuli to influence cellular growth and proliferation. This downstream effector of target of rapamycin (TOR) signaling cascade is known to be directly activated by TOR- kinase mediated hydrophobic motif (HM) phosphorylation at Threonine 412 (T412). Selective loss of this phosphorylation by inactivation of TOR kinase or activation/recruitment of a phosphatase has accordingly been implicated in mediating inhibition by rapamycin.Findings
We present evidence that baculovirus driven expression of S6K1 in insect cells (Sf9) fails to activate the enzyme and instead renders it modestly active representing 4-6 folds less activity than its fully active mammalian counterpart. Contrary to the contention that viral infection activates TOR signaling pathway, we report that BVr enzyme fails to exhibit putative TOR dependent phosphorylation at the HM and the resultant phosphorylation at the activation loop (AL) of the enzyme, correlating with the level of activity observed. Surprisingly, the BVr enzyme continued to exhibit sensitivity to rapamycin that remained unaffected by mutations compromised for TOR phosphorylation (T412A) or deletions compromised for TOR binding (ΔNH 2-46/ΔCT104).Conclusions
These data together with the ability of the BVr enzyme to resist inactivation by phosphatases indicate that inhibition by rapamycin is not mediated by any phosphorylation event in general and TOR dependent phosphorylation in particular. 相似文献38.
Brains have to decide whether and how to respond to detected stimuli based on complex sensory input. The vinegar fly Drosophila melanogaster evaluates food sources based on olfactory cues. Here, we performed a behavioral screen using the vinegar fly and established the innate valence of 110 odorants. Our analysis of neuronal activation patterns evoked by attractive and aversive odorants suggests that even though the identity of odorants is coded by the set of activated receptors, the main representation of odorant valence is formed at the output level of the antennal lobe. The topographic clustering within the antennal lobe of valence-specific output neurons resembles a corresponding domain in the olfactory bulb of mice. The basal anatomical structure of the olfactory circuit between insects and vertebrates is known to be similar; our study suggests that the representation of odorant valence is as well. 相似文献
39.
This study describes identification of p16(INK4A) sequence variants and their potential association with esophageal squamous cell carcinoma (ESCC) in a high risk population from Kashmir, India. We report a novel 7 base pair exon 2 deletion in 22 out of 106 (~20%) surgically resected tumor samples. The deletion beginning at the second base of codon 103, results in a frame shift causing premature termination of the protein at codon 142, with structural and functional consequences predicted by insilico analysis. The described mutation is a previously unreported variant of p16(INK4A), perhaps representing a founder mutation unique to the population. 相似文献
40.