首页 | 本学科首页   官方微博 | 高级检索  
文章检索
  按 检索   检索词:      
出版年份:   被引次数:   他引次数: 提示:输入*表示无穷大
  收费全文   441篇
  免费   27篇
  2023年   6篇
  2022年   4篇
  2021年   11篇
  2020年   6篇
  2019年   11篇
  2018年   11篇
  2017年   10篇
  2016年   17篇
  2015年   24篇
  2014年   17篇
  2013年   32篇
  2012年   33篇
  2011年   28篇
  2010年   28篇
  2009年   20篇
  2008年   31篇
  2007年   25篇
  2006年   24篇
  2005年   19篇
  2004年   21篇
  2003年   9篇
  2002年   14篇
  2001年   9篇
  2000年   1篇
  1999年   5篇
  1998年   1篇
  1996年   3篇
  1995年   2篇
  1994年   5篇
  1993年   1篇
  1992年   4篇
  1990年   1篇
  1988年   4篇
  1987年   1篇
  1986年   1篇
  1985年   1篇
  1983年   2篇
  1982年   5篇
  1981年   1篇
  1980年   1篇
  1979年   4篇
  1976年   1篇
  1975年   1篇
  1974年   1篇
  1973年   3篇
  1972年   3篇
  1970年   1篇
  1969年   1篇
  1968年   2篇
  1967年   1篇
排序方式: 共有468条查询结果,搜索用时 531 毫秒
91.

Background

Direct sputum smear microscopy for tuberculosis (TB) lacks sensitivity for the detection of acid fast bacilli. Sputum pretreatment procedures may enhance sensitivity. We did a pilot study to compare the diagnostic accuracy and incremental yield of two short-duration (<1 hour) sputum pretreatment procedures to optimize direct smears among patients with suspected TB at a referral hospital in India.

Methodology/Findings

Blinded laboratory comparison of bleach and universal sediment processing (USP) pretreated centrifuged auramine smears to direct Ziehl-Neelsen (ZN) and direct auramine smears and to solid (Loweinstein-Jensen (LJ)) and liquid (BACTEC 460) culture. 178 pulmonary and extrapulmonary TB suspects were prospectively recruited during a one year period. Thirty six (20.2%) were positive by either solid or liquid culture. Direct ZN smear detected 22 of 36 cases and direct auramine smears detected 26 of 36 cases. Bleach and USP centrifugation detected 24 cases each, providing no incremental yield beyond direct smears. When compared to combined culture, pretreated smears were not more sensitive than direct smears (66.6% vs 61.1 (ZN) or 72.2 (auramine)), and were not more specific (92.3% vs 93.0 (ZN) or 97.2 (auramine).

Conclusions/Significance

Short duration sputum pretreatment with bleach and USP centrifugation did not increase yield as compared to direct sputum smears. Further work is needed to confirm this in a larger study and also determine if longer duration pre-treatment might be effective in optimizing smear microscopy for TB.  相似文献   
92.
The effects of yeheb (Cordeauxia edulis Hemsl.) leaf extract on feeding and oviposition by diamondback moth (DBM) (Plutella xylostella L.) and the behavior of DBM parasitoid, Cotesia vestalis (Haliday), were studied. Volatile organic compounds (VOCs) from the headspace of intact and DBM-damaged broccoli plants sprayed with yeheb extracts (YE) were also analyzed. Larval feeding and growth, and oviposition by adult DBM were strongly inhibited by the extract. Cotesia vestalis were attracted to volatile blends from intact or DBM-damaged broccoli plants sprayed with YE over intact plants sprayed with water or methanol. Analyses of VOCs in the headspace of broccoli plants revealed that both intact and DBM-damaged plants sprayed with YE showed remarkable differences in sesquiterpene compounds compared to intact control treatments. These combined negative effects of YE on DBM fitness together with positive effects on the parasitoid show that yeheb is a potential source of compounds for use in integrated pest management to control damage caused by DBM.  相似文献   
93.
A comparative study was carried out to evaluate the efficiency of different substrate materials along with macrophytes Typha latifolia and Cyperus rotundus in treating domestic wastewater intended for reuse in agriculture. The study was conducted over a period of 6 months with different retention times, and observations were taken twice per month. One-way analysis of variance and Tukey's Honest Significant Difference (HSD) tests were used to determine statistical significant differences between experimental columns. Treatment with T. latifolia planted in sand and mix substrate with 4-day retention time remarkably reduced the concentration of all bacterial pathogens. Log reductions observed were approximately 5.01 and 4.82 for total coliform (TC), 4.46 and 3.93 for Escherichia coli, and 5.52 and 5.48 for Shigella, respectively. Moreover, these treatments were also efficient in completely removing fecal coliform (FC) and Salmonella.Maximum parasites were removed by the treatment having sand alone as a substrate containing C. rotundus, but the difference was not significant from those planted with T. latifolia in the same substrate. The results suggest that T. latifolia aids in bacterial pathogens removal, while C. rotundus aids in parasites removal. Thus, wastewater treatment through constructed wetland having mix plantation of these species along with sand can eliminate some of the major enteric pathogens.  相似文献   
94.
TLR-4-mediated signaling is significantly impaired in macrophages from HIV(+) persons, predominantly owing to altered MyD88-dependent pathway signaling caused in part by constitutive activation of PI3K. In this study we assessed in these macrophages if the blunted increase in TLR-4-mediated TNF-α release induced by lipid A (LA) is associated with PI3K-induced upregulation of mammalian target of rapamycin (mTOR) activity. mTOR inhibition with rapamycin enhanced TLR-4-mediated TNF-α release, but suppressed anti-inflammatory IL-10 release. Targeted gene silencing of mTOR in macrophages resulted in LA-induced TNF-α and IL-10 release patterns similar to those induced by rapamycin. Rapamycin restored MyD88/IL-1R-associated kinase interaction in a dose-dependent manner. Targeted gene silencing of MyD88 (short hairpin RNA) and mTOR (RNA interference) inhibition resulted in TLR-4-mediated 70-kDa ribosomal protein S6 kinase activation and enhanced TNF-α release, whereas IL-10 release was inhibited in both silenced and nonsilenced HIV(+) macrophages. Furthermore, mTOR inhibition augmented LA-induced TNF-α release through enhanced and prolonged phosphorylation of ERK1/2 and JNK1/2 MAPK, which was associated with time-dependent MKP-1 destabilization. Taken together, impaired TLR-4-mediated TNF-α release in HIV(+) macrophages is attributable in part to mTOR activation by constitutive PI3K expression in a MyD88-dependent signaling pathway. These changes result in MAPK phosphatase 1 stabilization, which shortens and blunts MAPK activation. mTOR inhibition may serve as a potential therapeutic target to upregulate macrophage innate immune host defense responsiveness in HIV(+) persons.  相似文献   
95.
Ethanol exposure produces alterations in GABA(A) receptor function and expression associated with CNS hyperexcitability, but the mechanisms of these effects are unknown. Ethanol is known to increase both GABA(A) receptor α4 subunits and protein kinase C (PKC) isozymes in vivo and in vitro. Here, we investigated ethanol regulation of GABA(A) receptor α4 subunit expression in cultured cortical neurons to delineate the role of PKC. Cultured neurons were prepared from rat pups on postnatal day 0-1 and tested after 18?days. GABA(A) receptor α4 subunit surface expression was assessed using P2 fractionation and surface biotinylation following ethanol exposure for 4?h. Miniature inhibitory post-synaptic currents were measured using whole cell patch clamp recordings. Ethanol increased GABA(A) receptor α4 subunit expression in both the P2 and biotinylated fractions, while reducing the decay time constant in miniature inhibitory post-synaptic currents, with no effect on γ2 or δ subunits. PKC activation mimicked ethanol effects, while the PKC inhibitor calphostin C prevented ethanol-induced increases in GABA(A) receptor α4 subunit expression. PKCγ siRNA knockdown prevented ethanol-induced increases in GABA(A) receptor α4 subunit expression, but inhibition of the PKCβ isoform with PKCβ pseudosubstrate had no effect. We conclude that PKCγ regulates ethanol-induced alterations in α4-containing GABA(A) receptors.  相似文献   
96.
Tumor recurrence after chemotherapy or radiation remains a major obstacle to successful cancer treatment. A subset of cancer cells, termed cancer stem cells, can elude conventional treatments and eventually regenerate a tumor that is more aggressive. Despite the large number of studies, molecular events that govern the emergence of aggressive therapy-resistant cells with stem cell properties after chemotherapy are poorly defined. The present study provides evidence for the rare escape of tumor cells from drug-induced cell death, after an intermediate stay in a non-cycling senescent stage followed by unstable multiplication characterized by spontaneous cell death. However, some cells appear to escape and generate stable colonies with an aggressive tumor stem cell-like phenotype. These cells displayed higher CD133 and Oct-4 expression. Notably, the drug-selected cells that contained low levels of reactive oxygen species (ROS) also showed an increase in antioxidant enzymes. Consistent with this in vitro experimental data, we observed lower levels of ROS in breast tumors obtained after neoadjuvant chemotherapy compared with samples that did not receive preoperative chemotherapy. These latter tissues also expressed enhanced levels of ROS defenses with enhanced expression of superoxide dismutase. Higher levels of Oct-4 and CD133 were also observed in tumors obtained after neoadjuvant chemotherapy. Further studies provided evidence for the stabilization of Nrf2 due to reduced 26 S proteasome activity and increased p21 association as the driving signaling event that contributes to the transition from a high ROS quiescent state to a low ROS proliferating stage in drug-induced tumor stem cell enrichment.  相似文献   
97.
Actin-binding protein anillin (ANLN) is primarily involved in the cytokinesis and known to be dysregulated in many cancers including gastric cancer (GC). However, the regulation and clinical significance of ANLN in GC are far less clear. In the present study, we aimed to investigate the clinical significance and possible regulators of ANLN in GC. We have identified the Wnt/β-catenin associated regulation of ANLN by analyzing the in vitro perturbed β-catenin mRNA expression profiles. Investigating the gastric tumors from publicly available genome-wide mRNA expression profiles, we have identified the over expression of ANLN in gastric tumors. Association between ANLN expression and clinical characteristics of GC showed elevated expression in intestinal type GC. Performing a single sample prediction method across GC mRNA expression profiles, we have identified the over expression of ANLN in proliferative type gastric tumors compared to the invasive and metabolic type gastric tumors. In silico pathway prediction analysis revealed the association between Wnt/β-catenin signaling and ANLN expression in gastric tumors. Our results highlight that expression of a Wnt/β-catenin responsive gene ANLN in GC is a molecular predictor of intestinal and proliferative type gastric tumors.  相似文献   
98.
99.

Background

Studies conducted in Western countries suggest that early age at menarche and early age at menopause are both associated with increased total mortality, but limited data are available for Asian populations. We examined associations of age at menarche and natural menopause and duration of the reproductive span with mortality in a population-based cohort study of Chinese women.

Methods

We evaluated the effects of age at menarche, age at natural menopause, and number of reproductive years on total and cause-specific mortality among 31,955 naturally menopausal Chinese women who participated in the Shanghai Women''s Health Study, a population-based, prospective cohort study.

Results

A total of 3,158 deaths occurred during a median follow-up of 11.2 years. Results from Cox proportional hazards models showed that younger age at menopause (<46.64 years) was associated with higher risk of total mortality (Ptrend  = 0.02). Younger age at menarche (<14 years) was associated with higher risk of mortality from stroke (Ptrend  = 0.03) and diabetes (Ptrend = 0.02) but lower risk of mortality from respiratory system cancer (Ptrend  = 0.01). Women with a shorter reproductive span had lower risk of mortality from gynecological cancers (Ptrend = 0.03).

Conclusions

Our study found that menstrual characteristics are important predictors of mortality, suggesting an important role of sex hormones in biological aging.  相似文献   
100.
Among four cultivars of Brassica juncea L., viz., TM-4, TM-2, RH-30, and T-59, cv. T-59 was relatively more tolerant to nickel (Ni) toxicity based on the growth parameters, seedling vigor index, and metal tolerance index. Nickel application inhibited the activity of the nitrate-assimilating enzyme nitrate reductase in the roots, stem, and leaves, whereas the total organic nitrogen, proline, and activity of a polyamine-metabolizing enzyme, diamine oxidase, increased in this tolerant cultivar (T-59). It accumulated a good amount of Ni from the soil in its root and shoot (i.e., 6.0–6.51 μg Ni g?1 dry weight) during 2 months of cultivation with an 8.0 mM Ni supply in the soil. The data presented in this paper indicate that Ni tolerance and its removal by Indian mustard from subtropical Indian soil is cultivar dependent, possibly due to different genetic and physiological adaptations of the cultivars.  相似文献   
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号