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   2368篇
  免费   131篇
  国内免费   3篇
  2502篇
  2024年   1篇
  2023年   18篇
  2022年   33篇
  2021年   79篇
  2020年   37篇
  2019年   59篇
  2018年   51篇
  2017年   49篇
  2016年   68篇
  2015年   118篇
  2014年   136篇
  2013年   207篇
  2012年   236篇
  2011年   196篇
  2010年   129篇
  2009年   122篇
  2008年   132篇
  2007年   173篇
  2006年   122篇
  2005年   121篇
  2004年   113篇
  2003年   88篇
  2002年   73篇
  2001年   13篇
  2000年   13篇
  1999年   8篇
  1998年   17篇
  1997年   10篇
  1996年   16篇
  1995年   12篇
  1994年   10篇
  1993年   5篇
  1992年   3篇
  1991年   3篇
  1990年   1篇
  1989年   3篇
  1988年   2篇
  1987年   4篇
  1986年   2篇
  1984年   3篇
  1983年   1篇
  1982年   3篇
  1981年   1篇
  1979年   3篇
  1977年   1篇
  1976年   1篇
  1974年   1篇
  1970年   2篇
  1967年   2篇
  1956年   1篇
排序方式: 共有2502条查询结果,搜索用时 0 毫秒
11.
Poaceae pollen is one of the most prevalent aeroallergens causing allergenic reactions. The aim of this study was to characterise the grass pollen season in Tetouan during the years 2008–2010, to analyse the effect of some meteorological parameters on the incidence of the airborne Poaceae pollen, and to establish forecasting variables for daily pollen concentrations. Aerobiological sampling was undertaken over three seasons using the volumetric method. The pollen season started in April and showed the highest pollen index in May and June, when the maximum temperature ranged from 23 to 27 °C, respectively. The annual pollen score recorded varied from year to year between 2,588 and 5,404. The main pollen season lasted 114–173 days, with peak days occurring mainly in May; the highest concentration reached 308 pollen grains/m3. Air temperature was the most important meteorological parameter and correlated positively to daily pollen concentration increase. An increase in relative humidity and precipitation was usually related to a decrease in airborne pollen content. External validation of the models performed using data from 2011 showed that Poaceae pollen concentration can be highly predicted (64.2–78.6 %) from the maximum temperature, its mean concentration for the same day in other years, and its concentration recorded on the previous day. Sensitive patients suffering allergy to Poaceae pollen are at moderate to highest risk of manifesting allergic symptoms to grass pollen over 33–42 days. The results obtained provide new information on the quantitative contribution of the Poaceae pollen to the airborne pollen of Tetouan and on its temporal distribution. Airborne pollen can be surveyed and forecast in order to warn the atopic population.  相似文献   
12.
Objectives:The study aimed to determine the effect of adding a school-based plyometric training program (PMT) to physical education (PE) sessions on the strength, balance, and flexibility in primary school girls.Methods:Students from grades 3-6 were randomized equally to a plyometric or control group. In the control group, students took their regular PE classes twice a week. In the plyometric group, students performed PMT twice a week during the initial 20 minutes of every PE session. The Lido Linea closed kinetic chain isokinetic dynamometer, Star excursion balance test (SEBT), and sit-and-reach test were used to assess muscle strength, balance, and flexibility, respectively, before and after nine weeks of training.Results:The improvement in extension peak force (p=0.04) and extension total work (p<0.001) was more prevalent in the PMT group than in the control group. SEBT scores had improved significantly (p<0.05) for all directions in the PMT group, except in the anterior direction, which was highly significant (p<0.001). Hamstring and lower back flexibility had improved more in the PMT group than in the control group (p<0.001).Conclusion:Adding PMT to regular PE classes has a positive and notable effect on muscle strength, balance, and flexibility in primary school students.  相似文献   
13.
The conjugation of ubiquitin to proteins involves a cascade of activating (E1), conjugating (E2), and ubiquitin-ligating (E3) type enzymes that commonly signal protein destruction. In TGFbeta signaling the inhibitory protein Smad7 recruits Smurf2, an E3 of the C2-WW-HECT domain class, to the TGFbeta receptor complex to facilitate receptor degradation. Here, we demonstrate that the amino-terminal domain (NTD) of Smad7 stimulates Smurf activity by recruiting the E2, UbcH7, to the HECT domain. A 2.1 A resolution X-ray crystal structure of the Smurf2 HECT domain reveals that it has a suboptimal E2 binding pocket that could be optimized by mutagenesis to generate a HECT domain that functions independently of Smad7 and potently inhibits TGFbeta signaling. Thus, E2 enzyme recognition by an E3 HECT enzyme is not constitutively competent and provides a point of control for regulating the ubiquitin ligase activity through the action of auxiliary proteins.  相似文献   
14.
Heterocyclic analogues of squamocin have been semisynthesized by condensation reactions between squamocin-derived alpha-keto esters and heterodinucleophiles. The strong complex I inhibitory potency of squamocin-benzimidazole, a hybrid derivative, illustrates for the first time the functional analogy existing between the terminal butenolide of annonaceous acetogenins and heteroaromatic substructures of classic inhibitors of the enzyme. This finding supports the categorization of this atypical group of inhibitors as antagonists of the ubiquinone substrates. In addition, competition experiments of squamocin-benzimidazole versus squamocin and rolliniastatin-2 suggest that the binding of this hybrid inhibitor is responsible for a negative allosteric effect at the level of the first ubiquinone-binding site (A site) of mitochondrial complex I. This result supports the existence of a large cooperatively regulated inhibitor/ubiquinone-binding pocket located within the catalytic core of the enzyme, consisting of the association of the previously defined affinity sites A and B.  相似文献   
15.
16.
Summary A total of 242 metaphase plates from the peripheral blood of Nubian males living near Aswan, Egypt were studied with respect to the length of the Y chromosome and its location in metaphase spreads. The length of the Y was similar to that found in American Negroes, and the Y chromosome was peripherally located in 79 of the 242 cells.  相似文献   
17.
Loss of TP53 function through gene mutation is a critical event in the development and progression of colorectal cancer (CRC). Here we examined 51 primary CRC tumors from Tunisia for mutations in TP53 exons 4–9 using PCR-direct sequencing. TP53 status and mutation site/type were than correlated with nuclear protein accumulation, familial and clinicopathologic variables and data on KRAS mutations and microsatellite instability (MSI-H). The TP53 mutation analysis was possible in the tumor of 47 patients and a deleterious somatic mutation has been detected in 59.6 % of the patients (28/47) including 20 (71.4 %) missense mutations, 7 nonsense mutations (25 %) and 1 (3.6 %) frameshift mutation. 89.3 % (25/28) of the detected mutations were in exons 5–8, whereas 10.7 % (3/28) were in exon 4. Among the 27 non frameshift mutations, 89 % (24/27) were transitions and 11 % (3/27) were transversions. 64.3 % (18/27) of the altered amino acids corresponded to arginine. 74 % (20/27) were G>C to A>T transitions, and more than half (14/27) occur at hotspots codons with CpG sites. TP53 mutations correlated closely with TP53 accumulation (p = 0.0090) and inversely with MSI phenotype (p = 0.0658). A KRAS somatic mutation was identified in 25 % (7/28) of the TP53 mutated tumors. All these mutations were G>A transitions in codon 12 and all the tumors with combined alterations but one were distally located and MSS. In conclusion, frequency and types of TP53 mutations and correlations with TP53 protein accumulation, and MSI were as reported for non-Tunisian patients. However, no significant associations have been detected between TP53 mutations and clinicopathological data in Tunisian patients as previously reported.  相似文献   
18.
Many studies have been performed to assess the potential utility of natural products as immunomodulatory agents to enhance host responses against infection or to ameliorate immune-based pathologies. To determine whether eriodictyol has immunomodulatory effects and clarify which types of immune effector cells are stimulated in vitro, we investigated the stimulatory effect of eriodictyol on spleen cells isolated from BALB/c mice. Eriodictyol significantly stimulated splenocyte proliferation. However, only B lymphocytes (not T lymphocytes) could be stimulated by eriodictyol in a dose-related manner. Studies assessing potential effect of eriodictyol on innate immunity reported that eriodictyol enhanced significantly the killing activity of natural killer (NK) cells, T lymphocytes, and macrophages. We also demonstrated that eriodictyol inhibited nitric oxide (NO) production and lysosomal enzyme activity in murine peritoneal macrophages cultured ex-vivo, suggesting a potential anti-inflammatory effect in situ. Eriodictyol revealed also a cellular anti-oxidant activity in splenocytes and macrophages. Furthermore, eriodictyol increased catalase activity in spleen cells. From this data, it can be concluded that eriodictyol exhibited an immunomodulatory effect that could be ascribed in part to a cytoprotective effect related to its anti-oxidant activity.  相似文献   
19.
Exposure to air pollutants such as ozone (O(3)) induces airway hyperresponsiveness (AHR) and airway inflammation. Toll-like receptors (TLR) are first-line effector molecules in innate immunity to infections and signal via adapter proteins, including myeloid differentiation factor-88 (MyD88). We investigated the sensing of ozone by TLR2, TLR4, and MyD88. Ozone induced AHR in wild-type (WT) C57BL/6 mice, but AHR was absent in TLR2(-/-), TLR4(-/-), and MyD88(-/-) mice. Bronchoalveolar lavage neutrophilia induced by ozone was inhibited at 3 h but not at 24 h in TLR2(-/-) and TLR4(-/-) mice, while in MyD88(-/-) mice, this was inhibited at 24 h. We investigated the expression of inflammatory cytokines and TLR2, TLR4, and MyD88 in these mice. Ozone induced time-dependent increases in inflammatory gene expression of keratinocyte chemoattractant (KC) and IL-6 and of TLR2, TLR4, and MyD88 in WT mice. IL-6 and KC expression induced by ozone was inhibited in TLR2(-/-), TLR4(-/-), and MyD88(-/-) mice. Expression of MyD88 was increased in TLR2(-/-) and TLR4(-/-) mice, while induction of TLR2 or TLR4 was reduced in TLR2(-/-) and TLR4(-/-) mice, respectively. TLR2 and TLR4 mediate AHR induced by oxidative stress such as ozone, while the adapter protein MyD88, but not TLR2 or TLR4, is important in mediating ozone-induced neutrophilia. TLR2 and TLR4 may also be important in regulating the speed of neutrophilic response. Therefore, ozone may induce murine AHR and neutrophilic inflammation through the activation of the Toll-like receptor pathway that may sense noninfectious stimuli such as oxidative stress.  相似文献   
20.
Although recent progress in cardiovascular tissue engineering has generated great expectations for the exploitation of stem cells to restore cardiac form and function, the prospects of a common mass-produced cell resource for clinically viable engineered tissues and organs remain problematic. The refinement of stem cell culture protocols to increase induction of the cardiomyocyte phenotype and the assembly of transplantable vascularized tissue are areas of intense current research, but the problem of immune rejection of heterologous cell type poses perhaps the most significant hurdle to overcome. This article focuses on the potential advantages and problems encountered with various stem cell sources for reconstruction of the damaged or failing myocardium or heart valves and also discusses the need for integrating advances in developmental and stem cell biology, immunology and tissue engineering to achieve the full potential of cardiac tissue engineering. The ultimate goal is to produce 'off-the-shelf' cells and tissues capable of inducing specific immune tolerance.  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