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   1169篇
  免费   108篇
  1277篇
  2023年   10篇
  2022年   13篇
  2021年   29篇
  2020年   13篇
  2019年   15篇
  2018年   24篇
  2017年   17篇
  2016年   28篇
  2015年   54篇
  2014年   49篇
  2013年   71篇
  2012年   99篇
  2011年   87篇
  2010年   59篇
  2009年   38篇
  2008年   63篇
  2007年   65篇
  2006年   58篇
  2005年   49篇
  2004年   46篇
  2003年   43篇
  2002年   31篇
  2001年   24篇
  2000年   17篇
  1999年   23篇
  1998年   6篇
  1994年   4篇
  1993年   8篇
  1992年   16篇
  1991年   18篇
  1990年   9篇
  1989年   13篇
  1988年   9篇
  1987年   8篇
  1986年   10篇
  1985年   9篇
  1984年   8篇
  1983年   7篇
  1982年   8篇
  1981年   6篇
  1980年   10篇
  1979年   11篇
  1978年   12篇
  1977年   10篇
  1975年   6篇
  1973年   10篇
  1972年   6篇
  1971年   5篇
  1969年   4篇
  1966年   5篇
排序方式: 共有1277条查询结果,搜索用时 31 毫秒
21.
22.
Surfactant protein A (SP-A), a pulmonary collectin, plays a role in lung innate immune host defense. In this study the role of SP-A in regulating the inflammatory response to the flagella of Pseudomonas aeruginosa (PA) was examined. Intra-tracheal infection of SP-A deficient (SP-A-/-) C57BL/6 mice with wild type flagellated PA (PAK) resulted in an increase in inflammatory cell recruitment and increase in pro-inflammatory cytokines IL-6 and TNF-α, which was not observed with a mutant pseudomonas lacking flagella (fliC). SP-A directly bound flagellin, via the N-linked carbohydrate moieties and collagen-like domain, in a concentration dependent manner and enhanced macrophage phagocytosis of flagellin and wild type PAK. IL-1β was reduced in the lungs of SP-A-/- mice following PAK infection. MH-s cells, a macrophage cell line, generated greater IL-1β when stimulated with flagellin and SP-A. Historically flagella stimulate IL-1β production through the toll-like receptor 5 (TLR-5) pathway and through a caspase-1 activating inflammasome pathway. IL-1β expression became non-detectable in SP-A and flagellin stimulated MH-s cells in which caspase-1 was silenced, suggesting SP-A induction of IL-1β appears to be occurring through the inflammasome pathway. SP-A plays an important role in the pathogenesis of PA infection in the lung by binding flagellin, enhancing its phagocytosis and modifying the macrophage inflammatory response.  相似文献   
23.
So far, there has been a discrepancy between the velocities of kinesin-dependent microtubule motility measured in vitro and within cells. By changing ATP, Mg(2+), and kinesin concentrations, pH and ionic strength, we tried to find conditions that favour microtubule gliding across kinesin-covered glass surfaces. For porcine brain kinesin, we found that raising the molar Mg(2+)/ATP ratio can substantially elevate gliding velocity. Gliding became also faster after temperature elevation or lowering the number of kinesin molecules bound to the glass surface. The highest mean gliding velocity (1.8 microm/s+/-0.09 microm/s), approaching velocities measured for anterograde transport in vivo, was achieved by combination of favourable factors (2.5 m m ATP, 12.5 m m Mg(2+), 37 degrees C, 450 kinesin molecules/microm(2)).  相似文献   
24.
The aim of this study was to identify genes that influence iron regulation under varying dietary iron availability. Male and female mice from 20+ BXD recombinant inbred strains were fed iron-poor or iron-adequate diets from weaning until 4 mo of age. At death, the spleen, liver, and blood were harvested for the measurement of hemoglobin, hematocrit, total iron binding capacity, transferrin saturation, and liver, spleen and plasma iron concentration. For each measure and diet, we found large, strain-related variability. A principal-components analysis (PCA) was performed on the strain means for the seven parameters under each dietary condition for each sex, followed by quantitative trait loci (QTL) analysis on the factors. Compared with the iron-adequate diet, iron deficiency altered the factor structure of the principal components. QTL analysis, combined with PosMed (a candidate gene searching system) published gene expression data and literature citations, identified seven candidate genes, Ptprd, Mdm1, Picalm, lip1, Tcerg1, Skp2, and Frzb based on PCA factor, diet, and sex. Expression of each of these is cis-regulated, significantly correlated with the corresponding PCA factor, and previously reported to regulate iron, directly or indirectly. We propose that polymorphisms in multiple genes underlie individual differences in iron regulation, especially in response to dietary iron challenge. This research shows that iron management is a highly complex trait, influenced by multiple genes. Systems genetics analysis of iron homeostasis holds promise for developing new methods for prevention and treatment of iron deficiency anemia and related diseases.  相似文献   
25.
Naked mole-rats are highly social and strictly subterranean rodents that live in large communal colonies in sealed and chronically oxygen-depleted burrows. Brain slices from naked mole-rats show extreme tolerance to hypoxia compared to slices from other mammals, as indicated by maintenance of synaptic transmission under more hypoxic conditions and three fold longer latency to anoxic depolarization. A key factor in determining whether or not the cellular response to hypoxia is reversible or leads to cell death may be the elevation of intracellular calcium concentration. In the present study, we used fluorescent imaging techniques to measure relative intracellular calcium changes in CA1 pyramidal cells of hippocampal slices during hypoxia. We found that calcium accumulation during hypoxia was significantly and substantially attenuated in slices from naked mole-rats compared to slices from laboratory mice. This was the case for both neonatal (postnatal day 6) and older (postnatal day 20) age groups. Furthermore, while both species demonstrated more calcium accumulation at older ages, the older naked mole-rats showed a smaller calcium accumulation response than even the younger mice. A blunted intracellular calcium response to hypoxia may contribute to the extreme hypoxia tolerance of naked mole-rat neurons. The results are discussed in terms of a general hypothesis that a very prolonged or arrested developmental process may allow adult naked mole-rat brain to retain the hypoxia tolerance normally only seen in neonatal mammals.  相似文献   
26.
Previous studies demonstrated an enhanced beta(2)-adrenoceptor (AR) responsiveness in animals susceptible to ventricular fibrillation (VF) that was eliminated by exercise training. The present study investigated the effects of endurance exercise training on beta(1)-AR and beta(2)-AR expression in dogs susceptible to VF. Myocardial ischemia was induced by a 2-min occlusion of the left circumflex artery during the last minute of exercise in dogs with healed infarctions: 20 had VF [susceptible (S)] and 13 did not [resistant (R)]. These dogs were randomly assigned to either 10-wk exercise training [treadmill running; n = 9 (S) or 8 (R)] or an equivalent sedentary period [n = 11 (S) or 5 (R)]. Left ventricular tissue beta-AR protein and mRNA were quantified by Western blot analysis and RT-PCR, respectively. Because beta(2)-ARs are located in caveolae, caveolin-3 was also quantified. beta(1)-AR gene expression decreased ( approximately 5-fold), beta(2)-AR gene expression was not changed, and the ratio of beta(2)-AR to beta(1)-AR gene expression was significantly increased in susceptible compared with resistant dogs. beta(1)-AR protein decreased ( approximately 50%) and beta(2)-AR protein increased (400%) in noncaveolar fractions of the cell membrane in susceptible dogs. Exercise training returned beta(1)-AR gene expression to levels seen in resistant animals but did not alter beta(2)-AR protein levels in susceptible dogs. These data suggest that beta(1)-AR gene expression was decreased in susceptible dogs compared with resistant dogs and, further, that exercise training improves beta(1)-AR gene expression, thereby restoring a more normal beta-AR balance.  相似文献   
27.
Treatment of patients with undifferentiated and histologically confirmed neuroendocrine tumors (NET) usually includes chemotherapeutic intervention. This retrospective study evaluated the outcome of 2 such chemotherapies. 18 patients (11 males; age 56.2 ± 2.5) with proven progressive disease were enrolled (mean Ki-67 34 ± 5%). Patients were treated from 2005 to 2007 with regimen A (carboplatin, etoposide, paclitaxel), and from 2007 to 2009 with regimen B (cisplatin, etoposide). This change was due to low tolerability of regimen A. The standard imaging procedure was computed tomography. 8 patients underwent treatment with regimen A (mean 3.3 ± 0.7 courses). Due to severe side effects, 3 patients had their therapy prematurely discontinued. The treatment responses of 6 patients who received more than 1 course were: 0% complete response (CR), 17% partial response (PR), 50% stable disease (SD), and 33% progressive disease (PD). The median progression free survival (PFS) was 6.7 months (range 3.2-10.0). In contrast, 12 patients received regimen B (mean 3.8 ± 0.4 courses), and none of them dropped out because of side effects. The overall responses were: 0% CR, 17% PR, 42% SD, and 42% PD. The median PFS was 6.3 months (range 2.8-26.4). The response rates of both regimes were not statistically different. Patients who were treated with regimen B demonstrated comparable PFS and less severe side effects than patients who received regimen A. However, patients need to be aware of the relatively short PFS time. In order to improve therapeutic outcome of patients with progressive undifferentiated NET, new therapeutic approaches and larger multi-center studies are needed.  相似文献   
28.

Background

Intimate partner violence (IPV) and termination of pregnancy (TOP) are global health concerns, but their interaction is undetermined. The aim of this study was to determine whether there is an association between IPV and TOP.

Methods and Findings

A systematic review based on a search of Medline, Embase, PsycINFO, and Ovid Maternity and Infant Care from each database''s inception to 21 September 2013 for peer-reviewed articles of any design and language found 74 studies regarding women who had undergone TOP and had experienced at least one domain (physical, sexual, or emotional) of IPV. Prevalence of IPV and association between IPV and TOP were meta-analysed. Sample sizes ranged from eight to 33,385 participants. Worldwide, rates of IPV in the preceding year in women undergoing TOP ranged from 2.5% to 30%. Lifetime prevalence by meta-analysis was shown to be 24.9% (95% CI 19.9% to 30.6%); heterogeneity was high (I 2>90%), and variation was not explained by study design, quality, or size, or country gross national income per capita. IPV, including history of rape, sexual assault, contraceptive sabotage, and coerced decision-making, was associated with TOP, and with repeat TOPs. By meta-analysis, partner not knowing about the TOP was shown to be significantly associated with IPV (pooled odds ratio 2.97, 95% CI 2.39 to 3.69). Women in violent relationships were more likely to have concealed the TOP from their partner than those who were not. Demographic factors including age, ethnicity, education, marital status, income, employment, and drug and alcohol use showed no strong or consistent mediating effect. Few long-term outcomes were studied. Women welcomed the opportunity to disclose IPV and be offered help. Limitations include study heterogeneity, potential underreporting of both IPV and TOP in primary data sources, and inherent difficulties in validation.

Conclusions

IPV is associated with TOP. Novel public health approaches are required to prevent IPV. TOP services provide an opportune health-based setting to design and test interventions. Please see later in the article for the Editors'' Summary  相似文献   
29.
Investigations of the distribution and diversity of nitrogen-fixing microorganisms in natural environments have often relied on PCR amplification and sequence analysis of a portion of one of the key enzymes in nitrogen fixation, dinitrogenase reductase, encoded by nifH. Recent work has suggested that DNA macroarrays provide semiquantitative fingerprints of diversity within mixtures of nifH amplicons (G. F. Steward, B. D. Jenkins, B. B. Ward, and J. P. Zehr, Appl. Environ. Microbiol. 70:1455-1465, 2004). Here we report the application of macroarrays for a study in the Chesapeake Bay. Samples from different locations in the bay yielded distinct fingerprints. Analysis of replicates and samples from different locations by cluster analysis showed that replicates clustered together, whereas different samples formed distinct clusters. There was a correspondence between the hybridization pattern observed and that predicted from the distribution of sequence types in a corresponding clone library. Some discrepancies between the methods were observed which are likely a result of the high nifH sequence diversity in the Chesapeake Bay and the limited number of sequences represented on this version of the array. Analyses of sequences in the clone library indicate that the Chesapeake Bay harbors unique, phylogenetically diverse diazotrophs. The macroarray hybridization patterns suggest that there are spatially variable communities of diazotrophs, which have been confirmed by quantitative PCR methods (S. M. Short, B. D. Jenkins, and J. P. Zehr, Appl. Environ. Microbiol., in press). The results show that DNA macroarrays have great potential for mapping the spatial and temporal variability of functional gene diversity in the environment.  相似文献   
30.
Summary Two municipal sludges, one from a highly industrialized city, Chicago, Il, and another from a little industrialized, highly agricultural area, Tucson, AZ are compared for winter barley production on Pima c 1 (Typic torrifluvent). Both sludges were responsible for highly significant additions of Zn, Cu, Ni, Cd and P to the soil each year when applied at the rates of 100 mt/ha singly and 20 mt/ha each year for 4 years. Nitrogen responses for barley straw and grain were observed from both sludges. Tucson sludge appears to be attractive as a potential fertilizer, not only as an NPK source, but also for its organic matter and minimal amounts of heavy metals. The Chicago sludge with relatively high levels of heavy metals, particularly Cd, appears poorly suited as a fertilizer, if used for an extended period of time, because of the plant's tendency to take up elevated levels of certain heavy metals. Some parts of barley plants proved to be a better indicator of heavy metal uptake and concentration than others. The diagnostic-tissue test promises to be a useful tool to warn against undesirable accumulation of heavy metals. Fortunately, when compared with other plant parts, the heavy metal in grain was the least altered as a result of continued sewage sludge use on arid land. The soil's neutral to slightly alkaline pH and the presence of lime throughout the soil profile appeared to be critical factors in keeping plant uptake of heavy metals relatively low as compared with soils of other climates.  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