全文获取类型
收费全文 | 253篇 |
免费 | 17篇 |
国内免费 | 1篇 |
专业分类
271篇 |
出版年
2024年 | 1篇 |
2023年 | 6篇 |
2022年 | 9篇 |
2021年 | 12篇 |
2020年 | 5篇 |
2019年 | 7篇 |
2018年 | 10篇 |
2017年 | 6篇 |
2016年 | 14篇 |
2015年 | 20篇 |
2014年 | 13篇 |
2013年 | 13篇 |
2012年 | 25篇 |
2011年 | 22篇 |
2010年 | 13篇 |
2009年 | 12篇 |
2008年 | 10篇 |
2007年 | 15篇 |
2006年 | 8篇 |
2005年 | 10篇 |
2004年 | 6篇 |
2003年 | 5篇 |
2002年 | 4篇 |
2001年 | 5篇 |
2000年 | 1篇 |
1999年 | 1篇 |
1998年 | 1篇 |
1995年 | 3篇 |
1993年 | 1篇 |
1992年 | 1篇 |
1991年 | 1篇 |
1990年 | 1篇 |
1989年 | 3篇 |
1988年 | 1篇 |
1987年 | 1篇 |
1986年 | 1篇 |
1976年 | 1篇 |
1967年 | 1篇 |
1966年 | 2篇 |
排序方式: 共有271条查询结果,搜索用时 15 毫秒
51.
Tavoulari S Rizwan AN Forrest LR Rudnick G 《The Journal of biological chemistry》2011,286(4):2834-2842
In ion-coupled transport proteins, occupation of selective ion-binding sites is required to trigger conformational changes that lead to substrate translocation. Neurotransmitter transporters, targets of abused and therapeutic drugs, require Na(+) and Cl(-) for function. We recently proposed a chloride-binding site in these proteins not present in Cl(-)-independent prokaryotic homologues. Here we describe conversion of the Cl(-)-independent prokaryotic tryptophan transporter TnaT to a fully functional Cl(-)-dependent form by a single point mutation, D268S. Mutations in TnaT-D268S, in wild type TnaT and in serotonin transporter provide direct evidence for the involvement of each of the proposed residues in Cl(-) coordination. In both SERT and TnaT-D268S, Cl(-) and Na(+) mutually increased each other's potency, consistent with electrostatic interaction through adjacent binding sites. These studies establish the site where Cl(-) binds to trigger conformational change during neurotransmitter transport. 相似文献
52.
Apoptosis, or programmed cell death, plays a pivotal role in the elimination of unwanted, damaged, or infected cells in multicellular organisms and also in diverse biological processes, including development, cell differentiation, and proliferation. Apoptosis is a highly regulated form of cell death, and dysregulation of apoptosis results in pathological conditions including cancer, autoimmune and neurodegenerative diseases. The Bcl-2 family proteins are key regulators of apoptosis, which include both anti- and pro-apoptotic proteins, and a slight change in the dynamic balance of these proteins may result either in inhibition or promotion of cell death. Execution of apoptosis by various stimuli is initiated by activating either intrinsic or extrinsic pathways which lead to a series of downstream cascade of events, releasing of various apoptotic mediators from mitochondria and activation of caspases, important for the cell fate. In view of recent research advances about underlying mechanism of apoptosis, this review highlights the basics concept of apoptosis and its regulation by Bcl-2 family of protein. Furthermore, this review discusses the interplay of various apoptotic mediators and caspases to decide the fate of the cell. We expect that this review will add to the pool of basic information necessary to understand the mechanism of apoptosis which may implicate in designing better strategy to develop biomedical therapy to control apoptosis. 相似文献
53.
Sultana Juhara Mannan Mohammad Abul Kalam Azad Md. Ashik Ullah Abdullah Al Maruf Md. Israt Rayhan Mohammad Shamsul Ahsan Abul Hasnat 《Biological trace element research》2011,140(3):272-283
Drug abuser patients (n = 104), age ranging from 19 to 42 years, were randomly recruited to investigate the serum levels of trace elements (Cu, Zn,
Fe, and Mg), malondialdehyde (MDA), and immunoglobulin (IgG, IgA, and IgM) before and after clinical intervention. Control
group also included 104 healthy individuals. Blood samples were analyzed for determining trace elements, MDA, and immunoglobulin
using atomic absorption spectroscopy, Ultraviolet-Visible (UV-VIS) spectroscopy, and turbidimetry method, respectively. For
serum level of Zn and Fe, the differences between the groups (before intervention, after intervention, and control) were not
significant (p > 0.05). However, significant differences were found in serum copper levels between control group, drug abuser patients,
and before and after intervention (p < 0.05). The concentration of Mg was found to be significantly higher (p = 0.007) in drug abuser patients than the controls, and after intervention, the level was restored to control value. A displacement
of elemental homeostasis was observed in drug abuser patients compared to control, and it was improved after intervention.
An increase in serum concentration of MDA was found in drug abuser patients compared to control subjects (p > 0.05) but was not statistically significant. After intervention, the concentration was restored to control value (p > 0.05). The serum concentrations of IgA and IgM were found to be significantly higher (p < 0.05) in drug abuser patients before intervention than the controls, and the level tended to be restored to control level
after clinical intervention. Serum IgG level was found to be lower in drug abuser patients compared to controls and further
declined significantly (p < 0.05) after intervention. These findings may suggest a possible imbalance in the levels of micronutrients, antioxidants,
and immunoglobulin in drug abuser patients, which tend to be restored to control values after detoxification. 相似文献
54.
55.
Laura L. Hammitt John Ojal Mahfudh Bashraheil Susan C. Morpeth Angela Karani Ahsan Habib Dorota Borys David Goldblatt J. Anthony G Scott 《PloS one》2014,9(1)
Background
The impact on carriage and optimal schedule for primary vaccination of older children with 10-valent pneumococcal non-typeable Haemophilus influenzae protein-D conjugate vaccine (PHiD-CV) are unknown.Methods
600 Kenyan children aged 12–59 months were vaccinated at days 0, 60 and 180 in a double-blind randomized controlled trial according to the following vaccine sequence: Group A: PHiD-CV, PHiD-CV, diphtheria/tetanus/acellular pertussis vaccine (DTaP); Group B: PHiD-CV, DTaP, PHiD-CV; Group C: hepatitis A vaccine (HAV), DTaP, HAV. Nasopharyngeal carriage of Streptococcus pneumoniae was measured at five timepoints. In 375 subjects, serotype-specific responses were measured by 22F-inhibition ELISA and opsonophagocytic killing assays (OPA) one month after vaccination.Results
Following one dose of PHiD-CV, >90% of recipients developed IgG≥0.35 µg/mL to serotypes 1, 4, 5, 7F, 9V and 18C and OPA≥8 to serotypes 4, 7F, 9V, 18C, 23F. After a second dose >90% of recipients had IgG≥0.35 µg/mL to all vaccine serotypes and OPA≥8 to all vaccine serotypes except 1 and 6B. At day 180, carriage of vaccine-type pneumococci was 21% in recipients of two doses of PHiD-CV (Group A) compared to 31% in controls (p = 0.04). Fever after dose 1 was reported by 41% of PHiD-CV recipients compared to 26% of HAV recipients (p<0.001). Other local and systemic adverse experiences were similar between groups.Conclusions
Vaccination of children aged 12–59 months with two doses of PHiD-CV two to six months apart was immunogenic, reduced vaccine-type pneumococcal carriage and was well-tolerated. Administration of PHiD-CV would be expected to provide effective protection against vaccine-type disease.Trial Registration
ClinicalTrials.gov NCT01028326相似文献56.
Genetic variants in LEP,LEPR, and MC4R explain 30% of severe obesity in children from a consanguineous population 下载免费PDF全文
57.
58.
Khan Muhammad Tahir Zeb Muhammad Tariq Ahsan Hina Ahmed Abrar Ali Arif Akhtar Khalid Malik Shaukat Iqbal Cui Zhilei Ali Sajid Khan Anwar Sheed Ahmad Manzoor Wei Dong-Qing Irfan Muhammad 《Archives of microbiology》2021,203(1):59-66
Archives of Microbiology - Severe acute respiratory syndrome virus 2 (SARS-CoV-2) belongs to the single-stranded positive-sense RNA family. The virus contains a large genome that encodes four... 相似文献
59.
Nagib Ahsan Luca Fornelli Fares Z. Najar Sanjeewa Gamagedara Mohammad Robiul Hossan R. Shyama Prasad Rao Ujwal Punyamurtula Andrew Bauer Zhibo Yang Steven B. Foster Maureen A. Kane 《Proteomics》2023,23(20):2300150
Blood serum is arguably the most analyzed biofluid for disease prediction and diagnosis. Herein, we benchmarked five different serum abundant protein depletion (SAPD) kits with regard to the identification of disease-specific biomarkers in human serum using bottom-up proteomics. As expected, the IgG removal efficiency among the SAPD kits is highly variable, ranging from 70% to 93%. A pairwise comparison of database search results showed a 10%–19% variation in protein identification among the kits. Immunocapturing-based SAPD kits against IgG and albumin outperformed the others in the removal of these two abundant proteins. Conversely, non-antibody-based methods (i.e., kits using ion exchange resins) and kits leveraging a multi-antibody approach were proven to be less efficient in depleting IgG/albumin from samples but led to the highest number of identified peptides. Notably, our results indicate that different cancer biomarkers could be enriched up to 10% depending on the utilized SAPD kit compared with the undepleted sample. Additionally, functional analysis of the bottom-up proteomic results revealed that different SAPD kits enrich distinct disease- and pathway-specific protein sets. Overall, our study emphasizes that a careful selection of the appropriate commercial SAPD kit is crucial for the analysis of disease biomarkers in serum by shotgun proteomics. 相似文献
60.
Induction of autophagy by an oleanolic acid derivative,SZC017, promotes ROS‐dependent apoptosis through Akt and JAK2/STAT3 signaling pathway in human lung cancer cells 下载免费PDF全文