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   1083篇
  免费   111篇
  国内免费   1篇
  1195篇
  2023年   8篇
  2022年   12篇
  2021年   24篇
  2020年   20篇
  2019年   28篇
  2018年   33篇
  2017年   29篇
  2016年   42篇
  2015年   73篇
  2014年   67篇
  2013年   60篇
  2012年   73篇
  2011年   89篇
  2010年   39篇
  2009年   39篇
  2008年   62篇
  2007年   46篇
  2006年   63篇
  2005年   53篇
  2004年   46篇
  2003年   38篇
  2002年   32篇
  2001年   6篇
  2000年   8篇
  1999年   13篇
  1998年   8篇
  1997年   8篇
  1995年   6篇
  1994年   9篇
  1992年   8篇
  1991年   8篇
  1990年   5篇
  1989年   9篇
  1988年   6篇
  1987年   6篇
  1986年   4篇
  1985年   6篇
  1984年   4篇
  1983年   7篇
  1982年   11篇
  1981年   5篇
  1980年   8篇
  1979年   7篇
  1978年   7篇
  1976年   5篇
  1975年   7篇
  1974年   4篇
  1973年   7篇
  1972年   5篇
  1969年   4篇
排序方式: 共有1195条查询结果,搜索用时 0 毫秒
81.
There are several conflicting hypothesis that deal with the influence of flooding in the natural river–floodplain systems. According to the Flood Pulse Concept, the flood pulses are not considered to be a disturbance, while some recent studies have proven that floods can be a disturbance factor of phytoplankton development. In order to test whether flooding acts as a disturbance factor in the shallow Danubian floodplain lake (Lake Sakadaš), phytoplankton dynamics was investigated during two different hydrological years—extremely dry (2003) without flooding and usually flooded (2004). A total of 18 phytoplankton functional groups were established. The sequence of phytoplankton seasonality can be summarized P/D → E (W1, W2) → C/P (only in potamophase) → S2/H1/SN/S1 → W1/W2 → P/D. The canonical correspondence analysis (CCA) demonstrated that the water level was a significant environmental variable in 2004. Due to the higher total biomass of Bacillariophyceae established under potamophase conditions, floodings in the early spring seem to be a stimulating factor for phytoplankton development. On the other hand, the flood pulses in May and June had dilution effects on nutrients, so that a significantly lower phytoplankton biomass was established indicating that flooding pulses can be regarded as a disturbance event. Such conditions supported diatom development (D, P, C species) and prolonged its dominance in the total phytoplankton biomass. A long-lasting Cyanoprokaryota bloom (various filamentous species—S1, S2, SN and H1 representatives) with very high biomass characterized the limnophase (dry conditions) in summer and autumn of both years. In-lake variables (lake morphology, internal loadings of nutrients from sediments, light conditions) seem to be important for the appearance of Cyanoprokaryota bloom. The equilibrium phase was found during the Cyanoprokaryota bloom only in the extremely dry year. This study showed that depending on the time scale occurrence, flood pulses can be a stimulating or a disturbance factor for phytoplankton development in Lake Sakadaš. Handling editor: J. Padisak  相似文献   
82.

Background

Burden of disease estimates are widely used for priority setting in public health and disability-adjusted life years are a powerful “currency” nowadays. However, disability weights, which capture the disability incurred by a typical patient of a certain condition, are fundamental to such burden calculation and their determination remains a widely debated issue.

Methodology

A cross-sectional epidemiological survey was conducted in the recently established Taabo health demographic surveillance system (HDSS) in south-central Côte d''Ivoire, to provide new, population-based evidence on the disability caused by schistosomiasis and soil-transmitted helminthiasis. Parasitological results from stool, urine, and blood examinations were juxtaposed to quality of life (QoL) questionnaire results from 187 adults. A multivariable linear regression model with stepwise backward elimination was used to identify significant associations, considering also sociodemographic characteristics obtained from the Taabo HDSS database.

Principal Findings

Prevalences for hookworm, Plasmodium spp., Trichuris trichiura, Schistosoma haematobium and Schistosoma mansoni were 39.0%, 18.2%, 2.7%, 2.1% and 2.1%, respectively. S. mansoni and T. trichiura infections of any intensity reduced the participants'' self-rated QoL by 16 points (95% confidence interval (CI): 4–29 points) and 13 points (95% CI: 1–24 points), respectively, on a scale from 0 (worst QoL) to 100 points (best QoL). The only other statistically significant effect was a 1-point (95% CI: 0.1–2 points) increase on the QoL scale per one unit increase in a calculated wealth index.

Conclusions/Significance

We found consistent and significant results on the negative effects of schistosomiasis and soil-transmitted helminthiasis on adults'' self-rated QoL, also when taking sociodemographic characteristics into account. Our results warrant further investigation on the disability incurred by helmintic infections and the usefulness of generic QoL questionnaires in this endeavor.  相似文献   
83.
L-Myo-inositol 1-phosphate synthase (INPS EC 5.5.1.4) catalyzes the conversion of D-glucose 6-phosphate to L-myo-inositol 1-phosphate. INPS is a key enzyme involved in the biosynthesis of phytate which is a common form of stored phosphates in higher plants. The present study monitored the increase of INPS expression in Azolla filiculoides resulting from exposure to inorganic phosphates, metals and salt stress. The expression of INPS was significantly higher in Azolla plants that were grown in rich mineral growth medium than those maintained on nutritional growth medium. The expression of INPS protein and corresponding mRNA increased in plants cultured in minimal nutritional growth medium when phosphate or Zn2+, Cd2+ and NaCl were added to the growth medium. When employing rich mineral growth medium, INPS protein content increased with the addition of Zn2+, but decreased in the presence of Cd2+ and NaCl. These results indicated that accumulation of phytate in Azolla is a result of the intensified expression of INPS protein and mRNA, and its regulation may be primarily derived by the uptake of inorganic phosphate, and Zn2+, Cd2+ or NaCl.  相似文献   
84.
In this article, we describe a novel autosomal recessive ichthyosis with hypotrichosis syndrome, characterized by congenital ichthyosis associated with abnormal hair. Using homozygosity mapping, we mapped the disease locus to 11q24.3-q25. We screened the ST14 gene, which encodes matriptase, since transplantation of skin from matriptase(-/-)-knockout mice onto adult athymic nude mice has been shown elsewhere to result in an ichthyosislike phenotype associated with almost complete absence of erupted pelage hairs. Mutation analysis revealed a missense mutation, G827R, in the highly conserved peptidase S1-S6 domain. Marked skin hyperkeratosis due to impaired degradation of the stratum corneum corneodesmosomes was observed in the affected individuals, which suggests that matriptase plays a significant role in epidermal desquamation.  相似文献   
85.
86.
In type 1 diabetes, inflammatory and immunocompetent cells enter the islet and produce proinflammatory cytokines such as interleukin-1β (IL-1β), IL-12, tumor necrosis factor-α (TNFα) and interferon-γ (IFNγ); each contribute to β-cell destruction, mediated in part by nitric oxide. Inhibitors of histone deacetylases (HDAC) are used commonly in humans but also possess antiinflammatory and cytokine-suppressing properties. Here we show that oral administration of the HDAC inhibitor ITF2357 to mice normalized streptozotocin (STZ)-induced hyperglycemia at the clinically relevant doses of 1.25-2.5 mg/kg. Serum nitrite levels returned to nondiabetic values, islet function improved and glucose clearance increased from 14% (STZ) to 50% (STZ + ITF2357). In vitro, at 25 and 250 nmol/L, ITF2357 increased islet cell viability, enhanced insulin secretion, inhibited MIP-1α and MIP-2 release, reduced nitric oxide production and decreased apoptosis rates from 14.3% (vehicle) to 2.6% (ITF2357). Inducible nitric oxide synthase (iNOS) levels decreased in association with reduced islet-derived nitrite levels. In peritoneal macrophages and splenocytes, ITF2357 inhibited the production of nitrite, as well as that of TNFα and IFNγ at an IC(50) of 25-50 nmol/L. In the insulin-producing INS cells challenged with the combination of IL-1β plus IFNγ, apoptosis was reduced by 50% (P < 0.01). Thus at clinically relevant doses, the orally active HDAC inhibitor ITF2357 favors β-cell survival during inflammatory conditions.  相似文献   
87.
The role of cytochrome c (Cyt c) in caspase activation has largely been established from mammalian cell-culture studies, but much remains to be learned about its physiological relevance in situ. The role of Cyt c in invertebrates has been subject to considerable controversy. The Drosophila genome contains distinct cyt c genes: cyt c-p and cyt c-d. Loss of cyt c-p function causes embryonic lethality owing to a requirement of the gene for mitochondrial respiration. By contrast, cyt c-d mutants are viable but male sterile. Here, we show that cyt c-d regulates developmental apoptosis in the pupal eye. cyt c-d mutant retinas show a profound delay in the apoptosis of superfluous interommatidial cells and perimeter ommatidial cells. Furthermore, there is no apoptosis in mutant retinal tissues for the Drosophila homologues of apoptotic protease-activating factor 1 (Ark) and caspase 9 (Dronc). In addition, we found that cyt c-d--as with ark and dronc-regulates scutellar bristle number, which is known to depend on caspase activity. Collectively, our results indicate a role of Cyt c in caspase regulation of Drosophila somatic cells.  相似文献   
88.
Maturation of dendritic cells (DC) is critical for the induction of Ag-specific immunity. Ag-loaded DC matured with LPS, which mediates its effects by binding to Toll-like receptor 4 (TLR4), induce Ag-specific CTL in vitro and in vivo in animal models. However, clinical use of LPS is limited due to potential toxicity. Therefore, we sought to mimic the maturation-inducing effects of LPS on DC by stimulating TLR4-mediated signaling in the absence of exogenous LPS. We developed a constitutively active TLR4 (caTLR4) and demonstrated that transfection of human DC with RNA encoding caTLR4 led to IL-12 and TNF-alpha secretion. Transfection with caTLR4 RNA also induced a mature DC phenotype. Functionally, transfection of DC with caTLR4 RNA enhanced allostimulation of CD4(+) T cells. DC transfected with RNA encoding the MART (Melan-A/MART-1) melanoma Ag were then used to stimulate T cells in vitro. Cotransfection of these DC with caTLR4 RNA enhanced the generation of MART-specific CTL. This CTL activity was superior to that seen when DC maturation was induced using either LPS or a standard mixture of cytokines (TNF-alpha, IL-6, IL-1beta, and PGE(2)). We conclude that transfection of DC with RNA encoding a functional signaling protein, such as caTLR4, may provide a new tool for studying TLR signaling in DC and may be a promising approach for the induction of DC maturation for tumor immunotherapy.  相似文献   
89.
Injuries to the postnatal skeleton are naturally repaired through successive steps involving specific cell types in a process collectively termed “bone regeneration”. Although complex, bone regeneration occurs through a series of well-orchestrated stages wherein endogenous bone stem cells play a central role. In most situations, bone regeneration is successful; however, there are instances when it fails and creates non-healing injuries or fracture nonunion requiring surgical or therapeutic interventions. Transplantation of adult or mesenchymal stem cells (MSCs) defined by the International Society for Cell and Gene Therapy (ISCT) as CD105+CD90+CD73+CD45-CD34-CD14orCD11b-CD79αorCD19-HLA-DR- is being investigated as an attractive therapy for bone regeneration throughout the world. MSCs isolated from adipose tissue, adipose-derived stem cells (ADSCs), are gaining increasing attention since this is the most abundant source of adult stem cells and the isolation process for ADSCs is straightforward. Currently, there is not a single Food and Drug Administration (FDA) approved ADSCs product for bone regeneration. Although the safety of ADSCs is established from their usage in numerous clinical trials, the bone-forming potential of ADSCs and MSCs, in general, is highly controversial. Growing evidence suggests that the ISCT defined phenotype may not represent bona fide osteoprogenitors. Transplantation of both ADSCs and the CD105- sub-population of ADSCs has been reported to induce bone regeneration. Most notably, cells expressing other markers such as CD146, AlphaV, CD200, PDPN, CD164, CXCR4, and PDGFRα have been shown to represent osteogenic sub-population within ADSCs. Amongst other strategies to improve the bone-forming ability of ADSCs, modulation of VEGF, TGF-β1 and BMP signaling pathways of ADSCs has shown promising results. The U.S. FDA reveals that 73% of Investigational New Drug applications for stem cell-based products rely on CD105 expression as the “positive” marker for adult stem cells. A concerted effort involving the scientific community, clinicians, industries, and regulatory bodies to redefine ADSCs using powerful selection markers and strategies to modulate signaling pathways of ADSCs will speed up the therapeutic use of ADSCs for bone regeneration.  相似文献   
90.
An enzyme-linked immunosorbent assay (ELISA) for the detection of IgG antibodies to Babesia microti antigen was developed. B. microti antigens were harvested from experimentally infected hamster blood and used as a coating antigen. The sensitivity and specificity of the IgG ELISA relative to immunofluorescent antibody assay (IFA) testing was 95.5% and 94.1%, respectively. According to the receiver operating characteristic curve analysis, the area under the curve was 0.987. No cross-reactivity of serum samples collected from patients infected with Toxoplasma gondii, Borrelia burgdorferi, Anaplasma phagocytophilum, Bartonella quintana, Dengue virus, or West Nile virus was detected. Cross-reactivity was observed with one of 35 sera from patients infected with Bartonella henselae. These results indicate that the established ELISA methods could be utilized as an accurate measure for the clinical diagnosis of human babesiosis.  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