全文获取类型
收费全文 | 997篇 |
免费 | 76篇 |
专业分类
1073篇 |
出版年
2023年 | 7篇 |
2022年 | 35篇 |
2021年 | 53篇 |
2020年 | 23篇 |
2019年 | 41篇 |
2018年 | 38篇 |
2017年 | 24篇 |
2016年 | 41篇 |
2015年 | 43篇 |
2014年 | 49篇 |
2013年 | 69篇 |
2012年 | 55篇 |
2011年 | 72篇 |
2010年 | 38篇 |
2009年 | 31篇 |
2008年 | 59篇 |
2007年 | 41篇 |
2006年 | 32篇 |
2005年 | 33篇 |
2004年 | 27篇 |
2003年 | 16篇 |
2002年 | 13篇 |
2001年 | 25篇 |
2000年 | 14篇 |
1999年 | 19篇 |
1998年 | 7篇 |
1997年 | 6篇 |
1996年 | 8篇 |
1995年 | 9篇 |
1994年 | 3篇 |
1993年 | 11篇 |
1992年 | 7篇 |
1991年 | 22篇 |
1990年 | 9篇 |
1989年 | 14篇 |
1988年 | 5篇 |
1987年 | 6篇 |
1986年 | 4篇 |
1985年 | 5篇 |
1984年 | 3篇 |
1982年 | 3篇 |
1981年 | 7篇 |
1980年 | 4篇 |
1979年 | 4篇 |
1978年 | 5篇 |
1976年 | 5篇 |
1973年 | 4篇 |
1972年 | 5篇 |
1971年 | 3篇 |
1966年 | 3篇 |
排序方式: 共有1073条查询结果,搜索用时 15 毫秒
21.
Umair Mahmood Muhammad Imran Salma Iqbal Naik Huma Arshad Cheema Anjum Saeed Muhammad Arshad Saqib Mahmood 《Gene》2012
Type I galactosemia is an inborn error resulting from mutations on both alleles of the GALT gene, which leads to the absence or deficiency of galactose-1-phosphate uridyltranseferase (GALT), the second of three enzymes catalyzing the conversion of galactose into glucose. On the basis of residual GALT activity, Type I galactosemia is classified into severe “Classical” and mild “Duarte” phenotypes. Classical galactosemia is frequently associated with S135L, Q188R and K285N mutations in the GALT gene. The functionally neutral N314D variation in the GALT gene is associated with Duarte galactosemia and is widespread among various worldwide populations. The present study aimed at detecting S135L, Q188R and K285N mutations and the N314D variant in the GALT gene by PCR using amplification refractory mutation system (ARMS). ARMS assays were established using standard DNA samples and were used for 8 galactosemia patients and 190 unrelated normal subjects all of Pakistani origin. S135L and K285N mutations were present neither in galactosemia patients nor in normal subjects. Only one galactosemia patient carried Q188R mutation that was in homozygous state. However, the N314D variant was frequently found both in affected (7 out of 16 alleles) and normal subjects (55 out of 380 alleles). This finding indicates that Duarte allele D314 might be far more common in Pakistani population than in European and North American ones. 相似文献
22.
J. Mocco Aqeela Afzal Saeed Ansari Annemarie Wolfe Kenneth Caldwell E S. Connolly Edward W. Scott 《PloS one》2014,9(1)
Background
Hematopoietic stem cells mobilize to the peripheral circulation in response to stroke. However, the mechanism by which the brain initiates this mobilization is uncharacterized.Methods
Animals underwent a murine intraluminal filament model of focal cerebral ischemia and the SDF1-A pathway was evaluated in a blinded manner via serum and brain SDF1-A level assessment, Lin−/Sca1+ cell mobilization quantification, and exogenous cell migration confirmation; all with or without SDF1-A blockade.Results
Bone marrow demonstrated a significant increase in Lin−/Sca1+ cell counts at 24 hrs (272±60%; P<0.05 vs sham). Mobilization of Lin−/Sca1+ cells to blood was significantly elevated at 24 hrs (607±159%; P<0.05). Serum SDF1-A levels were significant at 24 hrs (Sham (103±14), 4 hrs (94±20%, p = NS) and 24 hrs (130±17; p<0.05)). Brain SDF1-A levels were significantly elevated at both 4 hrs and 24 hrs (113±7 pg/ml and 112±10 pg/ml, respectively; p<0.05 versus sham 76±11 pg/ml). Following administration of an SDF1-A antibody, Lin−/Sca1+ cells failed to mobilize to peripheral blood following stroke, despite continued up regulation in bone marrow (stroke bone marrow cell count: 536±65, blood cell count: 127±24; p<0.05 versus placebo). Exogenously administered Lin−/Sca1+ cells resulted in a significant reduction in infarct volume: 42±5% (stroke alone), versus 21±15% (Stroke+Lin−/Sca1+ cells), and administration of an SDF1-A antibody concomitant to exogenous administration of the Lin−/Sca1+ cells prevented this reduction. Following stroke, exogenously administered Lin−/Sca1+ FISH positive cells were significantly reduced when administered concomitant to an SDF1-A antibody as compared to without SDF1-A antibody (10±4 vs 0.7±1, p<0.05).Conclusions
SDF1-A appears to play a critical role in modulating Lin−/Sca1+ cell migration to ischemic brain. 相似文献23.
Hamid Irannejad Mohsen Amini Fariba Khodagholi Niloufar Ansari Solaleh Khoramian Tusi Mohammad Sharifzadeh Abbas Shafiee 《Bioorganic & medicinal chemistry》2010,18(12):4224-4230
The role of novel triazine derivatives against oxidative stress exerted by hydrogen peroxide on differentiated rat pheochromocytoma (PC12) cell line was examined and a consistent protection from H2O2-induced cell death, associated with a marked reduction in caspase-3 activation, was observed. Moreover, activation of NF-κB, a known regulator of a host of genes that involves in specific stress and inflammatory responses by H2O2, was greatly impaired by triazine pretreatment in differentiated PC12 cells. Neuroprotective effect of such compounds may represent a promising approach for treatment of neurodegenerative diseases. 相似文献
24.
25.
Kaur P Yousuf S Ansari MA Siddiqui A Ahmad AS Islam F 《Biological trace element research》2003,95(3):247-258
The effect of various doses of sodium tellurite (0.4, 0.8, and 2.0 mg/kg body weight, orally) on the activity of antioxidant
enzymes (glutathione peroxidase, glutathione reductase, glutathione-S-transferase, and catalase) and content of glutathione and thiobarbituric acid reactive substances (TBARSs) in the cerebrum,
cerebellum, and brainstem of male albino mice was studied after 15 d of treatment. All of the doses of tellurium (0.4, 0.8,
and 2.0 mg/kg body weight, orally) have depleted the activity of antioxidant enzymes and the content of glutathione dose dependently
in the cerebrum, cerebellum, and brainstem and it was significant with the dose of 2.0 mg/kg. On the other hand, the 2.0-mg/kg
dose of tellurium has significantly elevated the content of TBARSs in the cerebrum and cerebellum. The 0.8-mg/kg dose of tellurium
has significantly depleted the activities of glutathione peroxidase in the cerebrum and brainstem, glutathione-S-transferase in the cerebrum and cerebellum, catalase in the brainstem, and the content of glutathione in the cerebrum and
cerebellum. In contrast, this dose has significantly elevated the content of TBARSs in the cerebrum and cerebellum. However,
the depletion in the activity of glutathione reductase with various doses of sodium tellurite was not significant in any brain
part of mice. The result suggests that sodium tellurite differentially affects the antioxidant status within various parts
of the mice brain. 相似文献
26.
The Extracellular Matrix of Candida albicans Biofilms Impairs Formation of Neutrophil Extracellular Traps 总被引:1,自引:0,他引:1
Chad J. Johnson Jonathan Cabezas-Olcoz John F. Kernien Steven X. Wang David J. Beebe Anna Huttenlocher Hamayail Ansari Jeniel E. Nett 《PLoS pathogens》2016,12(9)
Neutrophils release extracellular traps (NETs) in response to planktonic C. albicans. These complexes composed of DNA, histones, and proteins inhibit Candida growth and dissemination. Considering the resilience of Candida biofilms to host defenses, we examined the neutrophil response to C. albicans during biofilm growth. In contrast to planktonic C. albicans, biofilms triggered negligible release of NETs. Time lapse imaging confirmed the impairment in NET release and revealed neutrophils adhering to hyphae and migrating on the biofilm. NET inhibition depended on an intact extracellular biofilm matrix as physical or genetic disruption of this component resulted in NET release. Biofilm inhibition of NETosis could not be overcome by protein kinase C activation via phorbol myristate acetate (PMA) and was associated with suppression of neutrophil reactive oxygen species (ROS) production. The degree of impaired NET release correlated with resistance to neutrophil attack. The clinical relevance of the role for extracellular matrix in diminishing NET production was corroborated in vivo using a rat catheter model. The C. albicans pmr1Δ/Δ, defective in production of matrix mannan, appeared to elicit a greater abundance of NETs by scanning electron microscopy imaging, which correlated with a decreased fungal burden. Together, these findings show that C. albicans biofilms impair neutrophil response through an inhibitory pathway induced by the extracellular matrix. 相似文献
27.
The ability of the freshwater alga, Chlorella kessleri, to maintain a carbon concentrating mechanism when grown at acid pH was investigated. The alga grows over the pH range 4.0–9.0 and was found to take up bicarbonate and CO2 actively when grown at pH 6.0. However, when grown at acid pH (below 5.5), it does not have active CO2 uptake. The acidotolerant species maintained an internal pH of 6.1–7.5 over the external pH range 4.5–7.5, thus the pH difference between the cell interior and the external medium was large enough to allow for the diffusive uptake of CO2 at acid external pH. Mass spectrometric monitoring of O2 and CO2 fluxes by suspensions of C. kessleri, grown at acid pH, and maintained at pH 7.5 showed that the rates of O2 evolution did not exceed those of CO2 uptake. The final CO2 compensation concentrations of 14.0–17.7 µM reached by photosynthetic cells were above the CO2 equilibrium concentration in the external medium, indicating a lack of active CO2 uptake at acid pH. Chlorella kessleri accumulated CO2 with internal concentrations that were 9.9, 18.7 and 22.7‐fold that of the external medium for cells grown, respectively, at pH 4.5, 5.0 and 5.5. The ability of C. kessleri cells to accumulate high intracellular concentrations of inorganic carbon at acid pH would provide a sufficiently high concentration of CO2 at the active site of Rubisco thus allowing the alga to maintain growth rates similar to those at alkaline pH. 相似文献
28.
Siddappa N. Byrareddy Dawn Little Ann E. Mayne Francois Villinger Aftab A. Ansari 《PloS one》2015,10(10)
Lectin-like molecules and their receptors are cell surface molecules that have been shown to play a role in either facilitating infection or serving as transporters of HIV/SIV in vivo. The role of these lectin-like molecules in the pathogenesis of HIV/SIV infection continues to be defined. In efforts to gain further insight on the potential role of these lectin-like molecules, our laboratory generated monoclonal antibodies (mAb) against the human analogs of rhesus macaque CD200, CD200R and Mincle, since the rhesus macaques are accepted as the most reliable animal model to study human HIV infection. The characterization of the cell lineages from the blood and various tissues of rhesus macaques that express these lectin-like molecules are described herein. Among the mononuclear cells, the cells of the myeloid lineage of rhesus macaques are the predominant cell lineages that express readily detectable levels of CD200, CD200R and Mincle that is similar to the expression of Siglec-1 and Siglec-3 reported by our laboratory earlier. Subset analysis revealed that a higher frequency of the CD14+/CD16- subset from normal rhesus macaques express CD200, CD200R and Mincle. Differences in the frequencies and density of expression of these molecules by the gated population of CD14+ cells from various tissues are noted with PBMC and bone marrow expressing the highest and the mononuclear cells isolated from the colon and ileum expressing the lowest levels. While a significant frequency of pDCs and mDCs express Siglec-1/Siglec-3, a much lower frequency expresses CD200, CD200R and Mincle in PBMCs from rhesus macaques. The mAb against CD200 and CD200R but not Mincle appear to inhibit the infection of macrophage tropic SIV/SHIV in vitro. We conclude that these mAbs may have potential to be used as adjunctive therapeutic agents to control/inhibit SIV/HIV infection. 相似文献
29.
Among the known biomarkers, chemokines, secreted by activated macrophages and T cells, attract groups of immune cells to the site of infection and may determine the clinical outcome. Association studies of CCL-2/MCP-1 -2518 A/G functional SNP linked to high and low phenotypes with tuberculosis disease susceptibility have shown conflicting results in tuberculosis. Some of these differences could be due the variability of latent infection and recent exposure in the control groups. We have therefore carried out a detailed analysis of CCL-2 genotype SNP -2518 (A/G transition) with plasma CCL-2 levels and related these levels to tuberculin skin test positivity in asymptomatic community controls with no known exposure to tuberculosis and in recently exposed household contacts of pulmonary tuberculosis patients. TST positivity was linked to higher concentrations of plasma CCL2 (Mann Whitney U test; p = 0.004) and was more marked when the G allele was present in TST+ asymptomatic controls (A/G; p = 0.01). Recent exposure also had a significant effect on CCL-2 levels and was linked to the G allele (p = 0.007). Therefore association studies for susceptibility or protection from disease should take into consideration the PPD status as well as recent exposure of the controls group used for comparison. Our results also suggest a role for CCL-2 in maintaining the integrity of granuloma in asymptomatic individuals with latent infection in high TB burden settings. Therefore additional studies into the role of CCL-2 in disease reactivation and progression are warranted. 相似文献
30.