全文获取类型
收费全文 | 85篇 |
免费 | 4篇 |
专业分类
89篇 |
出版年
2021年 | 8篇 |
2020年 | 2篇 |
2019年 | 1篇 |
2018年 | 2篇 |
2017年 | 1篇 |
2016年 | 2篇 |
2015年 | 2篇 |
2014年 | 4篇 |
2013年 | 7篇 |
2012年 | 13篇 |
2011年 | 5篇 |
2010年 | 3篇 |
2009年 | 1篇 |
2008年 | 2篇 |
2007年 | 7篇 |
2006年 | 5篇 |
2005年 | 6篇 |
2004年 | 2篇 |
2003年 | 2篇 |
2002年 | 2篇 |
2001年 | 1篇 |
2000年 | 2篇 |
1999年 | 1篇 |
1998年 | 1篇 |
1997年 | 2篇 |
1993年 | 1篇 |
1990年 | 1篇 |
1988年 | 1篇 |
1987年 | 1篇 |
1983年 | 1篇 |
排序方式: 共有89条查询结果,搜索用时 0 毫秒
71.
72.
Isobel E. Bowles Emily H. Pool Benjamin S. Lancaster Emily K. Lawson Christopher P. Savas Zach J. Kartje Luke Severinac David H. Cho Mark R. Macbeth R. Jeremy Johnson Geoffrey C. Hoops 《Protein science : a publication of the Protein Society》2021,30(8):1554
Mycobacterium tuberculosis virulence is highly metal‐dependent with metal availability modulating the shift from the dormant to active states of M. tuberculosis infection. Rv0045c from M. tuberculosis is a proposed metabolic serine hydrolase whose folded stability is dependent on divalent metal concentration. Herein, we measured the divalent metal inhibition profile of the enzymatic activity of Rv0045c and found specific divalent transition metal cations (Cu2+ ≥ Zn2+ > Ni2+ > Co2+) strongly inhibited its enzymatic activity. The metal cations bind allosterically, largely affecting values for k cat rather than K M. Removal of the artificial N‐terminal 6xHis‐tag did not change the metal‐dependent inhibition, indicating that the allosteric inhibition site is native to Rv0045c. To isolate the site of this allosteric regulation in Rv0045c, the structures of Rv0045c were determined at 1.8 Å and 2.0 Å resolution in the presence and absence of Zn2+ with each structure containing a previously unresolved dynamic loop spanning the binding pocket. Through the combination of structural analysis with and without zinc and targeted mutagenesis, this metal‐dependent inhibition was traced to multiple chelating residues (H202A/E204A) on a flexible loop, suggesting dynamic allosteric regulation of Rv0045c by divalent metals. Although serine hydrolases like Rv0045c are a large and diverse enzyme superfamily, this is the first structural confirmation of allosteric regulation of their enzymatic activity by divalent metals. 相似文献
73.
Celik C Abali R Tasdemir N Guzel S Yuksel A Aksu E Yılmaz M 《Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology》2012,28(8):615-618
We aimed to analyze lipid parameters and determine the need for a 2-hour oral glucose tolerance test (OGTT) for the identification of IR and impaired glucose tolerance test (IGT) in subclinical hypothyroidism (SCH) women with and without polycystic ovary syndrome (PCOS). 20 patients with PCOS and SCH consisted of Group I and 39 patients with PCOS and normal thyroid function consisted of Group II and 53 healthy women with normal thyroid function consisted of Group III. Triglyceride levels were 143.26?±?99.86?mg/dL in group 1 and 88.56?±?37.56?mg/dL in group 2 and 83.71?±?31.94?mg/dL in group 3 which were statistically significant. Total cholesterol, HDL- cholesterol, LDL-cholesterol were found similar between the groups. Fasting insulin levels were 12.45?±?8.62 μU/mL in group 1 and 8.60?±?5.35 μU/mL in group 2 and 7.04?±?3.55 μU/mL in group 3 which were statistically significant (P?=?0.027). HOMA-IR were 2.92?±?2.34 in group 1 and 1.95?±?1.52 in group 2 and 1.60?±?0.86 in group 3 which were statistically significant (P?=?0.046). This study showed that women with PCOS and subclinical hypothyroidism should be evaluated for dyslipidemia and Insulin resistance. 相似文献
74.
Guzel S Kiziler L Aydemir B Alici B Ataus S Aksu A Durak H 《Biological trace element research》2012,145(1):23-32
Prostate cancer is known to be affected by the heavy metal levels and oxidative damage of the body, yet there are very few
studies which look into the way it occurs. The aim of this study was to determine whether blood and tissue lead (Pb), cadmium
(Cd), and selenium (Se) levels are associated with oxidative damage in the context of prostate cancer progression and development.
Seventy-nine patients comprising 25 patients with benign prostatic hypertrophy (BPH), 23 patients with malignant prostatic
carcinoma (malign Ca), 16 patients with low-grade prostatic intraepithelial neoplasia (LGPIN), and 15 patients with high-grade
prostatic intraepithelial neoplasia (HGPIN) diagnosed on the basis of their clinical profile, transrectal ultrasonography,
and histopathology were included in this study. Cd and Pb levels in whole blood were found to be increased in patients with
HGPIN compared with the BPH group; also, the levels of Cd in whole blood and tissue were found to be increasing in patients
with malign Ca, unlike BPH patients. Moreover, the levels of malondialdehyde (MDA) in plasma and tissue were significantly
increased in malign Ca, LGPIN, and HGPIN than those in BPH. However, the levels of tissue Pb were found to be decreasing in
BPH, unlike the malign Ca and HGPIN patients, and the levels of tissue protein carbonyls in malign Ca were significantly lower
than those in HGPIN. The levels of tissue reduced glutathione (GSH) in malign Ca were significantly lower than those in BPH.
Additionally, the levels of Se in serum and tissue in LGPIN were significantly lower than those in BPH. The serum Se levels
in HGPIN were also significantly lower than those in BPH and malign Ca groups. Furthermore, the concentrations of serum Se
in LGPIN were significantly lower than those in malign Ca. From the Pearson correlation analysis, there were significant positive
correlations between tissue Cd and MDA levels in malign Ca, LGPIN, and HGPIN and between the tissue Pb and tissue MDA and
protein carbonyl levels in malign Ca. Blood Pb and tissue Pb were also significantly positively correlated with plasma MDA
and protein carbonyl levels in malign Ca. In addition, blood Pb was significantly positively correlated with tissue MDA and
protein carbonyl levels in malign Ca, and a significant positive correlation was also found between blood Cd and plasma protein
carbonyls and tissue MDA in LGPIN. We observed that altered prooxidant–antioxidant balance and heavy metal levels may lead
to an increase in oxidative damage and may consequently play an important role in prostate carcinogenesis. These findings
indicate that changes in the levels of Pb, Cd, Se, MDA, protein carbonyls, and GSH in the blood and/or tissue are related
to the prostatic carcinoma development and progression, although triggering one of the mentioned changes is unknown; therefore,
further study is required to determine the exact steps of the process and clarify the roles of different substances in order
to obtain a more detailed explanation of the phenomenon. 相似文献
75.
76.
Juveniles of red porgy (Pagrus pagrus 1758 L.) were experimentallyproduced in RIOPESCA hatchery during Spring 1992–95. Wild broodstock,weighing from 500 to 1000 g, was caught and brought to the hatchery insummer 1991. They were placed in a 30 m3 rectangular outdoorbroodstock tank with a sea-water flow of 5 m3 per hour.Salinity ranged from 3.9 to 4.1%, temperature from 13 to25°C , the stocking density was 4 kg m–3,and the sex ratio was 1:1. The females spawned spontaneously in captivity producing approximately 200 000 eggs per kg of body weight. The percent offertilization was between 85–95%. Hatching was completed 85 hours later at 18 °C with a hatching percent of80–90%. The larvae were introduced into a 15 m3tank using green water (Nannochloropsis gaditana & Isochrysis galbana)and fed rotifers (Brachionus rotundiformis), Artemia salina nauplii andmetanauplii, and artificial food. After the end of the weaning period (day80 posthatch) the juveniles reached a weight of 1.4 g with a mean percentof survival of 10%. The fry were transferred to a cage site in which the growout proceeded without particular difficulties. The onlyproblem during growout was the skin coloration, that was darker than thatof wild porgies. Red porgies growth in our installations is satisfactory,with fry reaching 360 ± 12 g within 19 months, with a foodconversion rate of 1.8:1 , and a 6% mortality. 相似文献
77.
Shanks NF Savas JN Maruo T Cais O Hirao A Oe S Ghosh A Noda Y Greger IH Yates JR Nakagawa T 《Cell reports》2012,1(6):590-598
Highlights? Mass spectrometry identified proteins copurifying with AMPA and kainate receptors ? GSG1L is an AMPA-receptor-binding transmembrane protein ? GSG1L uniquely modulates AMPA receptor trafficking and channel gating ? GSG1L colocalizes with AMPA receptors at synapses 相似文献
78.
Savas S Azorsa DO Jarjanazi H Ibrahim-Zada I Gonzales IM Arora S Henderson MC Choi YH Briollais L Ozcelik H Tuzmen S 《PloS one》2011,6(4):e18306
Simvastatin and lovastatin are statins traditionally used for lowering serum cholesterol levels. However, there exists evidence indicating their potential chemotherapeutic characteristics in cancer. In this study, we used bioinformatic analysis of publicly available data in order to systematically identify the genes involved in resistance to cytotoxic effects of these two drugs in the NCI60 cell line panel. We used the pharmacological data available for all the NCI60 cell lines to classify simvastatin or lovastatin resistant and sensitive cell lines, respectively. Next, we performed whole-genome single marker case-control association tests for the lovastatin and simvastatin resistant and sensitive cells using their publicly available Affymetrix 125K SNP genomic data. The results were then evaluated using RNAi methodology. After correction of the p-values for multiple testing using False Discovery Rate, our results identified three genes (NRP1, COL13A1, MRPS31) and six genes (EAF2, ANK2, AKAP7, STEAP2, LPIN2, PARVB) associated with resistance to simvastatin and lovastatin, respectively. Functional validation using RNAi confirmed that silencing of EAF2 expression modulated the response of HCT-116 colon cancer cells to both statins. In summary, we have successfully utilized the publicly available data on the NCI60 cell lines to perform whole-genome association studies for simvastatin and lovastatin. Our results indicated genes involved in the cellular response to these statins and siRNA studies confirmed the role of the EAF2 in response to these drugs in HCT-116 colon cancer cells. 相似文献
79.
80.
This study was focused on the optimization of a new fermentation process for continuous gluconic acid production by the isolated yeast-like strain Aureobasidium pullulans DSM 7085 (isolate 70). Operational fermentation parameters were optimized in chemostat cultures, using a defined glucose medium. Different optima were found for growth and gluconic acid production for each set of operation parameters. Highest productivity was recorded at pH values between 6.5 and 7.0 and temperatures between 29 and 31 degrees C. A gluconic acid concentration higher than 230 g/L was continuously produced at residence times of 12 h. A steady state extracellular gluconic acid concentration of 234 g/L was measured at pH 6.5. 122% air saturation yielded the highest volumetric productivity and product concentration. The biomass-specific productivity increased steadily upon raising air saturation. An intracellular gluconic acid concentration of about 159 g/L (0.83 mol) was determined at 31 degrees C. This is to be compared with an extracellular concentration of 223 g/L (1.16 mol), which indicates the possible existence of an active transport system for gluconic acid secretion, or the presence of extracellular glucose oxidizing enzymes. The new process provides significant advantages over the traditional discontinuous fungi operations. The process control becomes easier, thus offering stable product quality and quantity. 相似文献