全文获取类型
收费全文 | 12312篇 |
免费 | 902篇 |
国内免费 | 365篇 |
专业分类
13579篇 |
出版年
2024年 | 26篇 |
2023年 | 102篇 |
2022年 | 289篇 |
2021年 | 387篇 |
2020年 | 289篇 |
2019年 | 351篇 |
2018年 | 403篇 |
2017年 | 318篇 |
2016年 | 424篇 |
2015年 | 680篇 |
2014年 | 792篇 |
2013年 | 868篇 |
2012年 | 1086篇 |
2011年 | 1021篇 |
2010年 | 646篇 |
2009年 | 548篇 |
2008年 | 735篇 |
2007年 | 650篇 |
2006年 | 536篇 |
2005年 | 494篇 |
2004年 | 512篇 |
2003年 | 397篇 |
2002年 | 315篇 |
2001年 | 256篇 |
2000年 | 211篇 |
1999年 | 217篇 |
1998年 | 98篇 |
1997年 | 67篇 |
1996年 | 55篇 |
1995年 | 65篇 |
1994年 | 61篇 |
1993年 | 47篇 |
1992年 | 82篇 |
1991年 | 76篇 |
1990年 | 55篇 |
1989年 | 50篇 |
1988年 | 36篇 |
1987年 | 27篇 |
1986年 | 30篇 |
1985年 | 28篇 |
1983年 | 19篇 |
1982年 | 15篇 |
1980年 | 27篇 |
1979年 | 21篇 |
1978年 | 14篇 |
1977年 | 18篇 |
1976年 | 13篇 |
1975年 | 15篇 |
1974年 | 17篇 |
1970年 | 12篇 |
排序方式: 共有10000条查询结果,搜索用时 17 毫秒
141.
Jin YC Kim KJ Kim YM Ha YM Kim HJ Yun UJ Bae KH Kim YS Kang SS Seo HG Lee JH Chang KC 《Experimental biology and medicine (Maywood, N.J.)》2008,233(10):1280-1288
Magnolol, an active component extracted from Magnolia officinalis, has been reported to have protective effect on ischemia and reperfusion (I/R)-induced injury in experimental animals. The aim of the present investigation was to further evaluate the mechanism(s) by which magnolol reduces I/R-induced myocardial injury in rats in vivo. Under anesthesia, left anterior descending (LAD) coronary artery was occluded for 30 min followed by reperfusion for 24 h (for infarct size and cardiac function analysis). In some experiments, reperfusion was limited to 1 h or 6 h for analysis of biochemical and molecular events. Magnolol and DMSO solution (vehicle) were injected intra-peritoneally 1 h prior to I/R insult. The infarct size was measured by TTC technique and heart function was monitored by Millar Catheter. Apoptosis related events such as p-ERK, p-Bad, Bcl-xl and cytochrome c expression were evaluated by Western blot analysis and myocardial caspase-3 activity was also measured. Magnolol (10 mg/kg) reduced infarct size by 50% (P < 0.01 versus vehicle), and also improved I/R-induced myocardial dysfunction. Left ventricular systolic pressure and positive and negative maximal values of the first derivative of left ventricular pressure (dP/dt) were significantly improved in magnolol-treated rats. Magnolol increased the expression of phosphor ERK and Bad which resulted in inhibition of myocardial apoptosis as evidenced by TUNEL analysis and DNA laddering experiments. Application of PD 98059, a selective MEK1/2 inhibitor, strongly antagonized the effect of magnolol. Taken together, we concluded that magnolol inhibits apoptosis through enhancing the activation of ERK1/2 and modulation of the Bcl-xl proteins which brings about reduction of infarct size and improvement of cardiac function in I/R-induced injury. 相似文献
142.
Lihua Kang Guowei Zhang Yaohua Yan Kaifu Ke Xinmin Wu Yilu Gao Jing Li Lin Zhu Qiyun Wu Zhengming Zhou 《Neurochemical research》2013,38(2):311-320
Heat shock protein A12B (HSPA12B) is the newest member of a recently defined subfamily of proteins distantly related to the 70-kDa family of heat shock proteins (HSP70) family. HSP70s play a crucial role in protecting cells, tissues, organs and animals from various noxious conditions. Here we studied the dynamic expression changes and localization of HSPA12B after middle cerebral artery occlusion (MCAO) with reperfusion induced ischemic insult processes in adult rats. Apoptosis, as indicated by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining, was also increased in the peri-ischemic cortex compared to non-ischemic hemisphere. The expression of HSPA12B was strongly induced in the ischemic hemisphere of MCAO reperfusion rats in vivo. In vitro studies indicated that the up-regulation of HSPA12B may be involved in oxygen-glucose deprivation-induced PC12 cell death. And knockdown of HSPA12B in cultured differentiated PC12 cells by siRNA showed that HSPA12B inhibited the expression of active caspase-3. Collectively, these results suggested that HSPA12B may be required for protecting neurons from ischemic insults. 相似文献
143.
Yong-ho Lee Mi Hyang Kown Kwang Joon Kim Eun Young Lee Daham Kim Byung-Wan Lee Eun Seok Kang Bong Soo Cha Hyun Chul Lee 《PloS one》2014,9(9)
Background
Glycated albumin (GA) has been increasingly used as a reliable index for short-term glycemic monitoring, and is inversely associated with β-cell function. Because the pathophysiologic nature of type 2 diabetes (T2D) is characterized by progressive decline in insulin secretion, the aim was to determine whether GA levels were affected by diabetes duration in subjects with T2D.Methods
To minimize the effect of glucose variability on GA, subjects with stably maintained HbA1c levels of <0.5% fluctuation across 6 months of measurements were included. Patients with newly diagnosed T2D (n = 1059) and with duration>1 year (n = 781) were recruited and categorized as New-T2D and Old-T2D, respectively. Biochemical, glycemic, and C-peptide parameters were measured.Results
GA levels were significantly elevated in HbA1c-matched Old-T2D subjects compared to New-T2D subjects. Duration of diabetes was positively correlated with GA, whereas a negative relationship was found with C-peptide increment (ΔC-peptide). Among insulin secretory indices, dynamic parameters such as ΔC-peptide were inversely related to GA (r = −0.42, p<0.001). Multiple linear regression analyses showed that duration of diabetes was associated with GA (standardized β coefficient [STDβ] = 0.05, p<0.001), but not with HbA1c (STDβ = 0.04, p<0.095). This association disappeared after additional adjustment with ΔC-peptide (STDβ = 0.02, p = 0.372), suggesting that β-cell function might be a linking factor of close relationship between duration of diabetes and GA values.Conclusions
The present study showed that GA levels were significantly increased in subjects with longer duration T2D and with decreased insulin secretory function. Additional caution should be taken when interpreting GA values to assess glycemic control status in these individuals. 相似文献144.
Sangita Choudhury Soochan Bae Qingen Ke Ji Yoo Lee Sylvia S. Singh René St-Arnaud Federica del Monte Peter M. Kang 《PloS one》2014,9(9)
Aim
Altered vitamin D signaling is associated with cardiac dysfunction, but the pathogenic mechanism is not clearly understood. We examine the mechanism and the role of vitamin D signaling in the development of cardiac dysfunction.Methods and Results
We analyzed 1α-hydroxylase (1α-OHase) knockout (1α-OHase−/−) mice, which lack 1α-OH enzymes that convert the inactive form to hormonally active form of vitamin D. 1α-OHase−/− mice showed modest cardiac hypertrophy at baseline. Induction of pressure overload by transverse aortic constriction (TAC) demonstrated exaggerated cardiac dysfunction in 1α-OHase−/− mice compared to their WT littermates with a significant increase in fibrosis and expression of inflammatory cytokines. Analysis of calcium (Ca2+) transient demonstrated profound Ca2+ handling abnormalities in 1α-OHase−/− mouse cardiomyocytes (CMs), and treatment with paricalcitol (PC), an activated vitamin D3 analog, significantly attenuated defective Ca2+ handling in 1α-OHase−/− CMs. We further delineated the effect of vitamin D deficiency condition to TAC by first correcting the vitamin D deficiency in 1α-OHase−/− mice, followed then by either a daily maintenance dose of vitamin D or vehicle (to achieve vitamin D deficiency) at the time of sham or TAC. In mice treated with vitamin D, there was a significant attenuation of TAC-induced cardiac hypertrophy, interstitial fibrosis, inflammatory markers, Ca2+ handling abnormalities and cardiac function compared to the vehicle treated animals.Conclusions
Our results provide insight into the mechanism of cardiac dysfunction, which is associated with severely defective Ca2+ handling and defective vitamin D signaling in 1α-OHase−/− mice. 相似文献145.
In vitro development of reconstructed porcine oocytes after somatic cell nuclear transfer 总被引:7,自引:0,他引:7
Koo DB Kang YK Choi YH Park JS Han SK Park IY Kim SU Lee KK Son DS Chang WK Han YM 《Biology of reproduction》2000,63(4):986-992
This study was designed to examine the developmental ability of porcine embryos after somatic cell nuclear transfer. Porcine fibroblasts were isolated from fetuses at Day 40 of gestation. In vitro-matured porcine oocytes were enucleated and electrically fused with somatic cells. The reconstructed eggs were activated using electrical stimulus and cultured in vitro for 6 days. Nuclear-transferred (NT) embryos activated at a field strength of 120 V/mm (11.6 +/- 1.6%) showed a higher developmental rate as compared to the 150-V/mm group (6.5 +/- 2.3%) (P: < 0.05), but the mean cell numbers of blastocysts were similar between the two groups. Rates of blastocyst development from NT embryos electrically pulsed at different times (2, 4, and 6 h) after electrofusion were 11.6 +/- 2.9, 6.6 +/- 2.3, and 8.1 +/- 3.3%, respectively. The mean cell numbers of blastocysts developed from NT embryos were gradually decreased (30.4 +/- 10.4 > 24.6 +/- 10.1 > 16.5 +/- 7.4 per blastocyst) as exposure time (2, 4, and 6 h) of nuclei to oocyte cytoplast before activation was prolonged. There was a significant difference in the cell number between the 2- and 6-h groups (P: < 0. 05). Nuclear-transferred embryos (9.4 +/- 0.9%) had a lower developmental rate than in vitro fertilization (IVF)-derived (21.4 +/- 1.9%) or parthenogenetic embryos (22.4 +/- 7.2%) (P: < 0.01). The mean cell number (28.9 +/- 11.4) of NT-derived blastocysts was smaller than that (38.6 +/- 10.4) of IVF-derived blastocysts (P: < 0. 05) and was similar to that (29.9 +/- 12.1) of parthenogenetic embryos. Our results suggest that porcine NT eggs using somatic cells after electrical activation have developmental potential to the blastocyst stage, although with smaller cell numbers compared to IVF embryos. 相似文献
146.
Park SM Yan BC Park JH Choi JH Yoo KY Lee CH Baek YY Kim YM Kang IJ Won MH 《Cellular and molecular neurobiology》2012,32(3):423-434
Tetanus toxin (TeT), an exotoxin, has been studied to cause tetanus in mammalian brains, and it can block the release of some
neurotransmitters and affect seizure propagation. In the present study, we investigated neuronal damage/death and glial changes
in the mouse hippocampus after systemic administration (intraperitoneal injection) of TeT 10 and 100 ng/kg. In both the 10
and 100 ng/kg TeT-treated groups, no neuronal death occurred in any subregions of the mouse hippocampus until 24 h post-treatment;
however, there were changes in glia in the hippocampus depending on time course and dosage. The morphology of GFAP-immunoreactive
astrocytes and Iba-1-immunoreactive microglia was apparently changed in the 100 ng/kg TeT treated-group compared to the 10 ng/kg
TeT treated-group. In the 100 ng/kg TeT treated-group, they were increased in size and their immunoreactivity was distinctively
increased from 12 h post-treatment. We also found that their protein levels were increased in the hippocampus at 12 h post-treatment
of 100 ng/kg TeT. In conclusion, these results indicate that the systemic administration of 100 ng/kg TeT induced a distinctive
microglia changes in the mouse hippocampus without any neuronal death/damage. 相似文献
147.
Woo Jong Choi Misun Kim Ji‐Youn Park Tae Jun Park Hee Young Kang 《Pigment cell & melanoma research》2015,28(1):51-60
Pleiotrophin (PTN) is a secreted heparin‐binding protein that is involved in various biological functions of cell growth and differentiation. Little is known about the effects of PTN on the melanocyte function and skin pigmentation. In this study, we investigated whether PTN would affect melanogenesis. PTN was expressed in melanocytes and fibroblasts of human skin. Transfection studies revealed that PTN decreased melanogenesis, probably through MITF degradation via Erk1/2 activation in melanocytes. The inhibitory action of PTN in pigmentation was further confirmed in ex vivo cultured skin and in the melanocytes cocultured with fibroblasts. These findings suggest that PTN is a crucial factor for the regulation of melanogenesis in the skin. 相似文献
148.
Introduction
Villin 1 is an actin-regulatory protein involved in the formation of microvilli of mammalian enterocytes. The microvilli, finger-like protrusions, are more abundant on the apical surfaces of gill ionocytes in various freshwater (FW) teleosts than in seawater (SW) fishes. However, the plasticity in the mechanisms of microvillus formation in the gill ionocytes are poorly understood, and the actin-regulatory proteins involved in the formation of microvilli have not been identified in fishes. The present study used the euryhaline medaka (Oryzias dancena) as a model to explore the role of a homolog of villin 1 in the actin-organization of cellular morphologies induced by decreasing salinities.Results
By ultrastructural observation, there are numerous actin filaments organized on the apical cortex of ion-absorptive ionocytes in the FW-acclimated medaka. From gills of the euryhaline medaka, we have identified the VILL sequence. The phylogenetic tree and functional domains suggest that VILL is the homolog of villin 1 in fishes. Immunofluorescence using a specific antibody revealed that VILL was specifically localized to the apical region of gill ionocytes along with microvilli in the FW medaka, but not in SW fish. The expression levels of Odvill mRNA and VILL protein were higher in the gills of the FW individuals than in the SW group and were induced when fish were transferred from SW to FW. A morpholino oligonucleotide for VILL knockdown eliminated the apical protrusions of ionocytes and pavement cells in the trunk epithelia of embryos.Conclusions
From a novel aspect of cytoskeletal functions, our findings highlighted the important role of VILL protein in the ionoregulation of aquatic vertebrates in response to different osmotic challenges. This study is the first to show that the expression of VILL is associated with the formation of microvilli in the absorptive ionocytes of a euryhaline fish. Loss-of-function experiments showed that the distribution of VILL may represent the molecular link between the cytoskeletal organization and cellular morphology of the absorptive ionocytes during hypoosmotic adaptation in aquatic vertebrates. 相似文献149.
150.
The net photosynthetic rate (P N), the sample room CO2 concentration (CO2S) and the intercellular CO2 concentration (C i) in response to PAR, of C3 (wheat and bean) and C4 (maize and three-colored amaranth) plants were measured. Results showed that photorespiration (R p) of wheat and bean could not occur at 2 % O2. At 2 % O2 and 0 μmol mol?1 CO2, P N can be used to estimate the rate of mitochondrial respiration in the light (R d). The R d decreased with increasing PAR, and ranged between 3.20 and 2.09 μmol CO2 m?2 s?1 in wheat. The trend was similar for bean (between 2.95 and 1.70 μmol CO2 m?2 s?1), maize (between 2.27 and 0.62 μmol CO2 m?2 s?1) and three-colored amaranth (between 1.37 and 0.49 μmol CO2 m?2 s?1). The widely observed phenomenon of R d being lower than R n can be attributed to refixation, rather than light inhibition. For all plants tested, CO2 recovery rates increased with increasing light intensity from 32 to 55 % (wheat), 29 to 59 % (bean), 54 to 87 % (maize) and 72 to 90 % (three-colored amaranth) at 50 and 2,000 μmol m?2 s?1, respectively. 相似文献