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991.
R Hashim AM Khatib G Enwere JK Park R Reyburn M Ali NY Chang DR Kim B Ley K Thriemer AL Lopez JD Clemens JL Deen S Shin C Schaetti R Hutubessy MT Aguado MP Kieny D Sack S Obaro AJ Shaame SM Ali AA Saleh L von Seidlein MS Jiddawi 《PLoS neglected tropical diseases》2012,6(7):e1743
Introduction
Mass vaccinations are a main strategy in the deployment of oral cholera vaccines. Campaigns avoid giving vaccine to pregnant women because of the absence of safety data of the killed whole-cell oral cholera (rBS-WC) vaccine. Balancing this concern is the known higher risk of cholera and of complications of pregnancy should cholera occur in these women, as well as the lack of expected adverse events from a killed oral bacterial vaccine.Methodology/Principal Findings
From January to February 2009, a mass rBS-WC vaccination campaign of persons over two years of age was conducted in an urban and a rural area (population 51,151) in Zanzibar. Pregnant women were advised not to participate in the campaign. More than nine months after the last dose of the vaccine was administered, we visited all women between 15 and 50 years of age living in the study area. The outcome of pregnancies that were inadvertently exposed to at least one oral cholera vaccine dose and those that were not exposed was evaluated. 13,736 (94%) of the target women in the study site were interviewed. 1,151 (79%) of the 1,453 deliveries in 2009 occurred during the period when foetal exposure to the vaccine could have occurred. 955 (83%) out of these 1,151 mothers had not been vaccinated; the remaining 196 (17%) mothers had received at least one dose of the oral cholera vaccine. There were no statistically significant differences in the odds ratios for birth outcomes among the exposed and unexposed pregnancies.Conclusions/Significance
We found no statistically significant evidence of a harmful effect of gestational exposure to the rBS-WC vaccine. These findings, along with the absence of a rational basis for expecting a risk from this killed oral bacterial vaccine, are reassuring but the study had insufficient power to detect infrequent events.Trial Registration
ClinicalTrials.gov NCT00709410相似文献992.
Young-Bin Shin Ji-Eun Lim Hyun-Seok Jin Kyung-Won Hong Bermseok Oh 《Genes & genomics.》2012,34(5):539-547
The 12q21 locus, which lies near the plasma membrane calcium-transporting ATPase 1 gene (ATP2B1), has one of the strongest associations with blood pressure and hypertension in Europeans and Asians. We performed an association analysis of the ATP2B isomers ATP2B2, ATP2B3, and ATP2B4 with blood pressure and hypertension in 7,551 Korean individuals and observed a link with ATP2B2 and ATP2B4. To examine the regulation of blood pressure by ATP2B, ATP2B1 and ATP2B4 mRNA was reduced in vascular smooth muscle cells by siRNA. The expression pattern of 23 ATP2B-related genes was analyzed by quantitative real-time PCR, which differed between treatment with ATP2B1 and ATP2B4 siRNA. The reduction inATP2B1 mRNA induced a significant change in mRNA levels in the calcium pump RYR1 and the ATP2B-binding protein HOMER1. Conversely, the decrease in ATP2B4 mRNA significantly altered mRNA expression of the calcium pump SLC8A1 and the ATP2B-binding proteins CASK and DLG4. These results suggest that blood pressure is differentially regulated through calcium signaling between ATP2B1 and ATP2B4. 相似文献
993.
JY Jung IY Kim YN Kim JS Kim JH Shin ZH Jang HS Lee GS Hwang JK Seong 《BMB reports》2012,45(7):419-424
High-fat diets (HFD) and high-carbohydrate diets (HCD)- induced obesity through different pathways, but the metabolic differences between these diets are not fully understood. Therefore, we applied proton nuclear magnetic resonance ((1)H NMR)-based metabolomics to compare the metabolic patterns between C57BL/6 mice fed HCD and those fed HFD. Principal component analysis derived from (1)H NMR spectra of urine showed a clear separation between the HCD and HFD groups. Based on the changes in urinary metabolites, the slow rate of weight gain in mice fed the HCD related to activation of the tricarboxylic acid cycle (resulting in increased levels of citrate and succinate in HCD mice), while the HFD affected nicotinamide metabolism (increased levels of 1-methylnicotineamide, nicotinamide-N-oxide in HFD mice), which leads to systemic oxidative stress. In addition, perturbation of gut microflora metabolism was also related to different metabolic patterns of those two diets. These findings demonstrate that (1)H NMR-based metabolomics can identify diet-dependent perturbations in biological pathways. 相似文献
994.
995.
Kim SH Lee IC Lim JH Moon C Bae CS Kim SH Shin DH Kim HC Kim JC 《Laboratory animal research》2012,28(1):11-16
This study was conducted to investigate the potential effects of α-chlorohydrin (ACH) on epididymal function and antioxidant system in male rats. The test chemical was administered to male rats by gavage at doses of 0, 3, 10, and 30 mg/kg/day for 7 days. Twenty-four male rats were randomly assigned to four experimental groups, with six rats in each group. Spermatotoxicity was assessed by measurement of reproductive organ weight, testicular sperm head count, epididymal sperm motility and morphology, histopathologic examination, and oxidative damage analysis in rats. At 30 mg/kg/day, an increase in the incidence of clinical signs, epididymis weight, and gross necropsy findings of the epididymis, a decrease in the sperm motility, and an increased incidence of histopathological changes of the epididymis were observed in a dose-dependent manner. At 10 mg/kg/day, an increased incidence of clinical signs and histopathological changes and decreased sperm motility were observed. In the oxidative damage analysis, an increase in the malondialdehyde concentration and a decrease in the glutathione content and glutathione peroxidase and catalase activities in the epididymal tissue were detected at ≥3 mg/kg/day. The results show that graded doses of ACH elicit depletion of the antioxidant defense system and that the spermatotoxicity of ACH may be due to the induction of oxidative stress. 相似文献
996.
997.
Translationally controlled tumor protein (TCTP), also termed P23 in human, belongs to a family of calcium- and tubulin-binding proteins, and it is generally regarded as a growth-regulating protein. Recently, Arabidopsis TCTP (AtTCTP) has been reported to function as an important growth regulator in plants. On the other hand, plant TCTP has been suggested to be involved in abiotic stress signaling such as aluminum, salt, and water deficit by a number of microarray or proteomic analyses. In this study, the biological functions of AtTCTP were investigated by using transgenic Arabidopsis plants overexpressing AtTCTP. Interestingly, AtTCTP overexpression enhanced drought tolerance in plants. The expression analysis showed that AtTCTP was expressed in guard cells as well as in actively growing tissues. Physiological studies of the overexpression lines showed increased ABA- and calcium-induced stomatal closure ratios and faster stomatal closing responses to ABA. Furthermore, in vitro protein-protein interaction analysis confirmed the interaction between AtTCTP and microtubules, and microtubule cosedimentation assays revealed that the microtubule binding of AtTCTP increased after calcium treatment. These results demonstrate that the overexpression of AtTCTP confers drought tolerance to plants by rapid ABA-mediated stomatal closure via the interaction with microtubules in which calcium binding enhances the interaction. Collectively, the present results suggest that the plant TCTP has molecular properties similar to animal TCTPs, such as tubulin- and calcium-binding, and that it functions in ABA-mediated stomatal movement, in addition to regulating the growth of plants. 相似文献
998.
Tae-Joon Shin Hyeon-Joong Kim Byeong-Jae Kwon Sun-Hye Choi Hyun-Bum Kim Sung-Hee Hwang Byung-Hwan Lee Sang-Mok Lee R. Suzanne Zukin Ji-Ho Park Hyoung-Chun Kim Hyewhon Rhim Joon-Hee Lee Seung-Yeol Nah 《Molecules and cells》2012,34(6):563-572
Ginseng has been shown to have memory-improving effects in human. However, little is known about the active components and the molecular mechanisms underlying its effects. Recently, we isolated novel lysophosphatidic acids (LPAs)-ginseng protein complex derived from ginseng, gintonin. Gintonin activates G protein-coupled LPA receptors with high affinity. Gintonin activated Ca2+-activated Clchannels in Xenopus oocytes through the activation of endogenous LPA receptor. In the present study, we investigated whether the activation of LPA receptor by gintonin is coupled to the regulation of N-methyl-d-aspartic acid (NMDA) receptor channel activity in Xenopus oocytes expressing rat NMDA receptors. The NMDA receptor-mediated ion current (I NMDA ) was measured using the two-electrode voltage-clamp technique. In oocytes injected with cRNAs encoding NMDA receptor subunits, gintonin enhanced I NMDA in a concentration-dependent manner. Gintonin-mediated I NMDA enhancement was blocked by Ki16425, an LPA1/3 receptor antagonist. Gintonin action was blocked by a PLC inhibitor, IP3 receptor antagonist, Ca2+ chelator, and a tyrosine kinase inhibitor. The site-directed mutation of Ser1308 of the NMDA receptor, which is phosphorylated by protein kinase C (PKC), to an Ala residue, or co-expression of receptor protein tyrosine phosphatase with the NMDA receptor attenuated gintonin action. Moreover, gintonin treatment elicited a transient elevation of [Ca2+]i in cultured hippocampal neurons and elevated longterm potentiation (LTP) in both concentration-dependent manners in rat hippocampal slices. Gintonin-mediated LTP induction was abolished by Ki16425. These results indicate that gintonin-mediated I NMDA potentiation and LTP induction in the hippocampus via the activation of LPA receptor might be responsible for ginseng-mediated improvement of memory-related brain functions. 相似文献
999.
Cho SY Jeong EM Lee JH Kim HJ Lim J Kim CW Shin DM Jeon JH Choi K Kim IG 《Molecules and cells》2012,33(3):235-241
The activation of transglutaminase 2 (TG2), an enzyme that catalyzes post-translational modifications of proteins, has been
implicated in apoptosis, cell adhesion and inflammatory responses. We previously reported that intracellular TG2 is activated
under oxidative stress conditions, such as ultraviolet irradiation, ischemia-reperfusion, and hypoxia. In this study, we examined
the effect of genotoxic stress on the intracellular activity of TG2 using doxorubicin which generates reactive oxygen species
that lead to double-strand breakage of DNA. We demonstrated that doxorubicin elicits the persistent activation of TG2. Doxorubicin-induced
TG2 activity was suppressed by treatment with caffeine at the early phase, N-acetylcysteine at the mid-phase, and EGTA at
the late phase. However, treatment with a blocking antibody against TGFβ or toll-like receptor 2 showed no effect on TG2 activity,
indicating that at least three different signaling pathways may be involved in the process of TG2 activation. In addition,
using MEF cells defective for TG2 and cells overexpressing an activesite mutant of TG2, we revealed that doxorubicin-induced
cell death is inversely correlated with TG2 activity. Our findings indicate that the persistent activation of TG2 by doxorubicin
contributes to cell survival, suggesting that the mechanism-based inhibition of TG2 may be a novel strategy to prevent drug-resistance
in doxorubicin treatment. 相似文献
1000.