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21.
Electromechanical integration of cardiomyocytes derived from human embryonic stem cells 总被引:1,自引:0,他引:1
Kehat I Khimovich L Caspi O Gepstein A Shofti R Arbel G Huber I Satin J Itskovitz-Eldor J Gepstein L 《Nature biotechnology》2004,22(10):1282-1289
Cell therapy is emerging as a promising strategy for myocardial repair. This approach is hampered, however, by the lack of sources for human cardiac tissue and by the absence of direct evidence for functional integration of donor cells into host tissues. Here we investigate whether cells derived from human embryonic stem (hES) cells can restore myocardial electromechanical properties. Cardiomyocyte cell grafts were generated from hES cells in vitro using the embryoid body differentiating system. This tissue formed structural and electromechanical connections with cultured rat cardiomyocytes. In vivo integration was shown in a large-animal model of slow heart rate. The transplanted hES cell-derived cardiomyocytes paced the hearts of swine with complete atrioventricular block, as assessed by detailed three-dimensional electrophysiological mapping and histopathological examination. These results demonstrate the potential of hES-cell cardiomyocytes to act as a rate-responsive biological pacemaker and for future myocardial regeneration strategies. 相似文献
22.
Snir M Kehat I Gepstein A Coleman R Itskovitz-Eldor J Livne E Gepstein L 《American journal of physiology. Heart and circulatory physiology》2003,285(6):H2355-H2363
Assessment of early ultrastructural development and cell-cycle regulation in human cardiac tissue is significantly hampered by the lack of a suitable in vitro model. Here we describe the possible utilization of human embryonic stem cell (ES) lines for investigation of these processes. With the use of the embryoid body (EB) differentiation system, human ES cell-derived cardiomyocytes at different developmental stages were isolated and their histomorphometric, ultrastructural, and proliferative properties were characterized. Histomorphometric analysis revealed an increase in cell length, area, and length-to-width ratio in late-stage EBs (>35 days) compared with early (10-21 days) and intermediate (21-35 days) stages. This was coupled with a progressive ultrastructural development from an irregular myofibrillar distribution to an organized sarcomeric pattern. Cardiomyocyte proliferation, assessed by double labeling with cardiac-specific antibodies and either [3H]thymidine incorporation or Ki-67 immunolabeling, demonstrated a gradual withdrawal from cell cycle. Hence, the percentage of positively stained nuclei in early-stage cardiomyocytes ([3H]thymidine: 60 +/- 10%, Ki-67: 54 +/- 23%) decreased to 36 +/- 7% and 9 +/- 16% in intermediate-stage EBs and to <1% in late-stage cardiomyocytes. In conclusion, a reproducible temporal pattern of early cardiomyocyte proliferation, cell-cycle withdrawal, and ultrastructural maturation was noted in this model. Establishment of this unique in vitro surrogate system may allow to examine the molecular mechanisms underlying these processes and to assess interventions aiming to modify these properties. Moreover, the detailed characterization of the ES cell-derived cardiomyocyte may be crucial for the development of future cell replacement strategies aiming to regenerate functional myocardium. 相似文献
23.
The Notch ligand Jagged-1 is able to induce maturation of monocyte-derived human dendritic cells 总被引:10,自引:0,他引:10
Weijzen S Velders MP Elmishad AG Bacon PE Panella JR Nickoloff BJ Miele L Kast WM 《Journal of immunology (Baltimore, Md. : 1950)》2002,169(8):4273-4278
Notch receptors play a key role in several cellular processes including differentiation, proliferation, and apoptosis. This study investigated whether the activation of Notch signaling would affect the maturation of dendritic cells (DCs). Direct stimulation of Notch signaling in DCs with a peptide ligand induced DC maturation, similar to LPS: DCs up-regulated maturation markers, produced IL-12, lost endocytosis capacity, and became able to activate allogeneic T cells. Furthermore, coculture of DCs with cells expressing Notch ligand Jagged-1 induced up-regulation of maturation markers, IL-12 production, T cell proliferative responses, and IFN-gamma production. Our data suggest that activation of Notch by Jagged-1 plays an important role in maturation of human DCs. Additionally, they reveal a novel role for Notch signaling in cell maturation events distal to the cell fate decision fork. These data may have important medical implications, since they provide new reagents to induce DC activity, which may be beneficial as adjuvants in situations where an immune response needs to be elicited, such as tumor immunotherapy. 相似文献
24.
Regulation of taurine transporter expression by NO in cultured human retinal pigment epithelial cells 总被引:4,自引:0,他引:4
Bridges Christy C.; Ola M. Shamsul; Prasad Puttur D.; El-Sherbeny Amira; Ganapathy Vadivel; Smith Sylvia B. 《American journal of physiology. Cell physiology》2001,281(6):C1825
Taurine is activelytransported at the retinal pigment epithelial (RPE) apical membrane inan Na+- and Cl-dependent manner. Diabetes mayalter the function of the taurine transporter. Because nitric oxide(NO) is a molecule implicated in the pathogenesis of diabetes, we askedwhether NO would alter the activity of the taurine transporter incultured ARPE-19 cells. The activity of the transporter was stimulatedin the presence of the NO donor 3-morpholinosydnonimine. Thestimulatory effects of 3-morpholinosydnonimine were not observed duringthe initial 16-h treatment; however, stimulation of taurine uptake waselevated dramatically above control values with 20- and 24-htreatments. Kinetic analysis revealed that the stimulation wasassociated with an increase in the maximal velocity of the transporterwith no significant change in the substrate affinity. The NO-induced increase in taurine uptake was inhibited by actinomycin D and cycloheximide. RT-PCR analysis and nuclear run-on assays provided evidence for upregulation of the transporter gene. This study providesthe first evidence of an increase in taurine transporter geneexpression in human RPE cells cultured under conditions of elevatedlevels of NO. 相似文献
25.
Amira Moussa Jihène Rejeb Asma Omezzine Lamia Rebhi Imen Boumaiza Slim Kacem Nabila Ben Rejeb Essia Boughzala Ahmed Ben Abdelaziz Ali Bouslama 《Biochemical genetics》2014,52(5-6):269-282
Haptoglobin (Hp) polymorphism generates three common human genotypes (Hp1-1, Hp2-1, and Hp2-2), having functional differences, related to the risk of development of cardiovascular diseases. These functions are a consequence of hemoglobin binding that leads to the synthesis of an antioxidant like ferritin. We explored the association of Hp polymorphism with significant coronary stenosis (SCS) and its severity within 400 Tunisian patients, using genotyping, biochemical parameters, and the Gensini score. After adjustments for age and gender, Hp2-2 was associated with the highest ferritin but the lowest Hp concentrations. After adjustments for confounding parameters, the OR of SCS associated with Hp2-2 was 1.74 (95% CI 1.18–2.58; p = 0.005). This effect was enhanced within diabetics (OR 1.90, 95% CI 1.11–3.24; p = 0.018), obese subjects (OR 1.98, 95% CI 1.10–4.86; p = 0.034), and smokers (OR 4.17, 95% CI 1.54–1.29; p = 0.005). The Hp2-2 genotype is associated with an increase in SCS especially in diabetics, the obese, and smokers. 相似文献
26.
Kalthoum Tizaoui Wajih Kaabachi Marwa Ouled Salah Amira Ben Amor Agnès Hamzaoui Kamel Hamzaoui 《Cellular immunology》2014
Recent genetic surveys have identified vitamin D receptor (VDR) as a susceptibility gene for several autoimmune diseases. This study was designed to investigate the association of VDR gene polymorphisms with Behçet’s disease (BD) and Rheumatoid arthritis (RA). A case–control study including 151 BD, 106 RA patients and an appropriate number of healthy control subjects were performed using polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) techniques. Association between TaqI polymorphism and BD was marginal under codominant and recessive models (P = 0.078 and P = 0.058, respectively). After stratification, we found evidence for a significant association between TaqI polymorphism and BD in the elderly subjects (P = 0.037). The minor ApaI a allele tended to confer an increased risk for BD susceptibility (P = 0.087). BD patients with VDR homozygous AA or aa genotypes were at increased risk for development of erythema nodosum (EN) skin manifestation (P = 0.038). No significant association was observed for VDR ApaI and TaqI polymorphisms with RA risk (P > 0.05). TaqI and ApaI polymorphisms might be modestly implicated in BD pathogenesis. They could be considered as potential biomarkers in BD rather than susceptibility genes. However, TaqI and ApaI seemed not to be implicated in RA pathogenesis. 相似文献
27.
Amira Sfaxi-Bousbih Abdelilah Chaoui Ezzedine El Ferjani 《Biological trace element research》2010,137(1):110-116
Seeds of bean (Phaseolus vulgaris L.) were germinated by soaking in distilled water or copper chloride solution. The relationships among copper excess treatment,
germination rate, dry weight, sugar contents, and carbohydrase activities in cotyledon were investigated. Heavy metal stress
provoked a diminution in germination rate and biomass mobilization, as compared with the control. A drastic disorder in soluble
sugars export, especially glucose and fructose liberation, was also imposed after exposure to excess copper. This restricted
the starch and sucrose breakdown in reserve tissue, as evidenced by the inhibition in the activities of α-amylase and invertase
isoenzymes (soluble acid, soluble neutral, cell wall-bound acid). 相似文献
28.
Gamal-Eldeen AM Djemgou PC Tchuendem M Ngadjui BT Tane P Toshifumi H 《Zeitschrift für Naturforschung. C, Journal of biosciences》2007,62(5-6):331-338
Phytochemical investigation of Cassia petersiana Bolle leaves afforded four new compounds, including two chromone derivatives, 7-acetonyl-5-hydroxy-2-methylchromone (petersinone 1, 1) and 7-(propan-2'-ol-l'-yl)-5-hydroxy-2-methylchromone (petersinone 2, 2), two benzoic acid derivatives, 5-methyl-3-(propan-2'-on-1'-yl) benzoic acid (petersinone 3, 3) and 5-(methoxymethyl)-3-(propan-2'-ol-1'-yl) benzoic acid (petersinone 4, 4), and glyceryl-1-tetracosanoate (6), in addition to the known compound sistosterol-3-beta-D-glycoside (5). The structures of these compounds were determined by comprehensive NMR studies, including DEPT, COSY, HMQC, HMBC, MS and IR. Compounds 1, 2, 5 and 6 were tested for antioxidant, anti-cancer and immunostimulatory properties. The biological investigations indicated that compound 6, among others, possessed the highest anti-cancer activity against hepatocellular carcinoma, immunoproliferative activity via induction of T-lymphocytes and macrophage proliferation, anti-inflammatory activity as indicated by NO inhibition, and antioxidant activity against DPPH radicals. Moreover, compound 5 was the most effective cytotoxic compound against breast carcinoma and stimulated a consistent immunoproliferative effect on lymphocytes and macrophages combined with strong NO inhibitory activity, while compound 1 was promising as immunoproliferative agent and may act as anti-inflammatory agent as a consequence of its NO inhibitory activity. 相似文献
29.
Troudi A Amara IB Samet AM Fetoui H Soudani N Guermazi F Boudawara T Zeghal N 《BioFactors (Oxford, England)》2011,37(6):429-438
Gibberellic acid (GA?) has been worldwide used in agriculture as a plant growth regulator. The purpose of this study is to assess the effects of GA? on the morphology and the thyroid hormone levels in adult rats and their suckling pups. Animals were given daily 200 ppm GA? in drinking water from the 14th day of pregnancy until day 14 after delivery. Compared with a control group, GA?-treated mothers and pups showed an increase in body and thyroid weights, a decrease in plasma FT? and FT? levels, which were more pronounced in pups than in their mothers. Thyroid iodine content was also decreased in pups. These biochemical modifications corresponded histologically; the majority of follicles had cubical epithelial cells, which surrounded empty vesicular cavities. Toxicity was objectified by a significant increase in plasma malondialdehyde, protein carbonyls, and advanced oxidation protein products levels in GA?-treated dams and their suckling pups; while, the activities of superoxide dismutase, catalase, and glutathione peroxidase were decreased in plasma of both dams and their pups. Moreover, a significant decline was observed in plasma glutathione, nonprotein thiols, and vitamin C levels. We conclude that GA? treatment affects thyroid function and plasma antioxidant status in adult rats and their progeny. 相似文献
30.
Roess AA Monroe BP Kinzoni EA Gallagher S Ibata SR Badinga N Molouania TM Mabola FS Mombouli JV Carroll DS MacNeil A Benzekri NA Moses C Damon IK Reynolds MG 《PLoS neglected tropical diseases》2011,5(10):e1356