全文获取类型
收费全文 | 869篇 |
免费 | 51篇 |
国内免费 | 4篇 |
专业分类
耳鼻咽喉 | 3篇 |
儿科学 | 20篇 |
妇产科学 | 119篇 |
基础医学 | 187篇 |
口腔科学 | 7篇 |
临床医学 | 43篇 |
内科学 | 166篇 |
皮肤病学 | 11篇 |
神经病学 | 43篇 |
特种医学 | 45篇 |
外科学 | 69篇 |
综合类 | 7篇 |
预防医学 | 78篇 |
眼科学 | 28篇 |
药学 | 42篇 |
肿瘤学 | 56篇 |
出版年
2022年 | 4篇 |
2021年 | 13篇 |
2020年 | 8篇 |
2019年 | 12篇 |
2018年 | 11篇 |
2017年 | 8篇 |
2016年 | 10篇 |
2015年 | 19篇 |
2014年 | 23篇 |
2013年 | 33篇 |
2012年 | 27篇 |
2011年 | 42篇 |
2010年 | 37篇 |
2009年 | 35篇 |
2008年 | 43篇 |
2007年 | 47篇 |
2006年 | 51篇 |
2005年 | 39篇 |
2004年 | 41篇 |
2003年 | 29篇 |
2002年 | 36篇 |
2001年 | 26篇 |
2000年 | 31篇 |
1999年 | 40篇 |
1998年 | 8篇 |
1997年 | 8篇 |
1996年 | 13篇 |
1995年 | 5篇 |
1994年 | 7篇 |
1992年 | 11篇 |
1991年 | 9篇 |
1990年 | 20篇 |
1989年 | 19篇 |
1988年 | 15篇 |
1987年 | 12篇 |
1986年 | 11篇 |
1985年 | 13篇 |
1984年 | 5篇 |
1983年 | 4篇 |
1982年 | 9篇 |
1979年 | 8篇 |
1978年 | 8篇 |
1976年 | 8篇 |
1974年 | 6篇 |
1973年 | 5篇 |
1972年 | 5篇 |
1970年 | 6篇 |
1969年 | 9篇 |
1968年 | 7篇 |
1966年 | 4篇 |
排序方式: 共有924条查询结果,搜索用时 31 毫秒
81.
82.
Sutter TR He XR Dimitrov P Xu L Narasimhan G George EO Sutter CH Grubbs C Savory R Stephan-Gueldner M Kreder D Taylor MJ Lubet R Patterson TA Kensler TW 《Molecular cancer therapeutics》2002,1(14):1283-1292
Microarray technology has greatly aided the identification of genes that are expressed differentially. Statistical analysis of such data by multiple comparisons procedures has been slow to develop, in part, because methods to cluster the results of such comparisons in biologically meaningful ways have not been available. We isolated and analyzed, by Northern blot and GeneChip, replicate liver RNA samples (n = 4/group) from rats fed with control diet or diet containing one of three chemopreventive compounds, selected because their pharmacological activities, including RNA expression response, are relatively well understood. We report on a classification tree, based on the results of nonparametric multiple comparisons, which results in the bipolar hierarchical clustering of genes in relation to their response to treatment. In addition to identifying treatment-responsive genes, application of this procedure to our test study identified the known pharmacological relationships among the treatment groups without supervision. Also, small treatment-specific subsets of genes were identified that may be indicative of additional pharmacophores present in the test compounds. 相似文献
83.
Martin?Dimitrov Pencho?Venkov Margarita?PeshevaEmail author 《Archives of toxicology》2011,85(1):67-74
In previous laboratory and environmental studies, the Ty1 short-term test showed positive responses (i.e. induced mobility
of the Ty1 retrotransposon) to carcinogenic genotoxins. Here, we provide evidence for a causal relationship between increased
level of reactive oxygen species and induction the mobility of the Ty1 retrotransposon. Results obtained in concentration
and time-dependent experiments after treatment, the tester cells with carcinogenic genotoxins [benzo(a)pyrene, benzo(a)anthracene,
ethylmethanesulfonate, formamide], free bile acids (chenodeoxycholic, lithocholic acids) and metals (arsenic, hexavelant chromium,
lead) showed a simultaneous increase in both cellular level of the superoxide anions and Ty1 retrotransposition rates. Treatment
with the noncarcinogenic genotoxins [benzo(e)pyrene, benzo(b)anthracen, anthracene], conjugated bile acids (taurodeoxycholic,
glycodeoxycholic acids) and metals (zinc, trivalent chromium) did not change significantly superoxide anions level and Ty1
retrotransposition rate. The induction by carcinogens of the Ty1 mobility seems to depend on the accumulation of superoxide
anions, since the addition of the scavenger N-acetylcysteine resulted in loss of both increased amount of superoxide anions and induced Ty1 retrotransposition. Increased
hydrogen peroxide levels are also involved in the induction of Ty1 retrotransposition rates in response to treatment with
carcinogenic genotoxins, as evidenced by disruption of YAP1 gene in the tester cells. It is concluded that the carcinogen-induced high level of reactive oxygen species play a primary
and key role in determination the selective response of Ty1 test to carcinogenic genotoxins. 相似文献
84.
Lin R Buijse L Dimitrov MR Dohmen P Kosol S Maltby L Roessink I Sinkeldam JA Smidt H Van Wijngaarden RP Brock TC 《Ecotoxicology (London, England)》2012,21(5):1550-1569
The ecological impact of the dithiocarbamate fungicide metiram was studied in outdoor freshwater microcosms, consisting of 14 enclosures placed in an experimental ditch. The microcosms were treated three times (interval 7 days) with the formulated product BAS 222 28F (Polyram®). Intended metiram concentrations in the overlying water were 0, 4, 12, 36, 108 and 324 μg a.i./L. Responses of zooplankton, macroinvertebrates, phytoplankton, macrophytes, microbes and community metabolism endpoints were investigated. Dissipation half-life (DT50) of metiram was approximately 1–6 h in the water column of the microcosm test system and the metabolites formed were not persistent. Multivariate analysis indicated treatment-related effects on the zooplankton (NOECcommunity = 36 μg a.i./L). Consistent treatment-related effects on the phytoplankton and macroinvertebrate communities and on the sediment microbial community could not be demonstrated or were minor. There was no evidence that metiram affected the biomass, abundance or functioning of aquatic hyphomycetes on decomposing alder leaves. The most sensitive populations in the microcosms comprised representatives of Rotifera with a NOEC of 12 μg a.i./L on isolated sampling days and a NOEC of 36 μg a.i./L on consecutive samplings. At the highest treatment-level populations of Copepoda (zooplankton) and the blue-green alga Anabaena (phytoplankton) also showed a short-term decline on consecutive sampling days (NOEC = 108 μg a.i./L). Indirect effects in the form of short-term increases in the abundance of a few macroinvertebrate and several phytoplankton taxa were also observed. The overall community and population level no-observed-effect concentration (NOECmicrocosm) was 12–36 μg a.i./L. At higher treatment levels, including the test systems that received the highest dose, ecological recovery of affected measurement endpoints was fast (effect period < 8 weeks). 相似文献
85.
86.
Parathyroid hormone receptor 2 (PTH2R) and its ligand, tuberoinfundibular peptide of 39 residues (TIP39) constitute a neuromodulator system implicated in endocrine and nociceptive regulation. We now describe the presence and distribution of the PTH2R and TIP39 in the brain of primates using a range of tissues and ages from macaque and human brain. In situ hybridization histochemistry of TIP39 mRNA, studied in young macaque brain, due to its possible decline beyond late postnatal ages, was present only in the thalamic subparafascicular area and the pontine medial paralemniscal nucleus. In contrast, in situ hybridization histochemistry in macaque identified high levels of PTH2R expression in the central amygdaloid nucleus, medial preoptic area, hypothalamic paraventricular and periventricular nuclei, medial geniculate, and the pontine tegmentum. PTH2R mRNA was also detected in several human brain areas by RT-PCR. The distribution of PTH2R-immunoreactive fibers in human, determined by immunocytochemistry, was similar to that in rodents, including dense fiber networks in the medial preoptic area, hypothalamic paraventricular, periventricular and infundibular (arcuate) nuclei, lateral hypothalamic area, median eminence, thalamic paraventricular nucleus, periaqueductal gray, lateral parabrachial nucleus, nucleus of the solitary tract, sensory trigeminal nuclei, medullary dorsal reticular nucleus, and dorsal horn of the spinal cord. Co-localization suggested that PTH2R fibers are glutamatergic, and that TIP39 may directly influence hypophysiotropic somatostatin containing and indirectly influence corticotropin releasing-hormone containing neurons. The results demonstrate that TIP39 and the PTH2R are expressed in the brain of primates in locations that suggest involvement in regulation of fear, anxiety, reproductive behaviors, release of pituitary hormones, and nociception. 相似文献
87.
Ekaterina Ivanova-Todorova Ivan Bochev Milena Mourdjeva Rumen Dimitrov Dimitar Bukarev Stanimir Kyurkchiev Petar Tivchev Iskra Altunkova Dobroslav Stanimirov Kyurkchiev 《Immunology letters》2009,126(1-2):37-42
Both mesenchymal stem cells (MSCs) and dendritic cells (DCs) are engaged in the regulation of the immune response parallel to their numerous functions.The main objective of this study was to compare the effects of mesenchymal stem cells isolated from human adipose tissue or human bone marrow on the expression of specific cell surface markers as well as the secretion of some cytokines by monocyte-derived dendritic cells. The set of methods used includes cell cultures, magnetic beads isolation of cells, flow cytometry, ELISA and proteome profiler kit assays. The results obtained show that MSCs isolated from human adipose tissue are more potent immunomodulators of differentiation of human DCs in comparison to the bone marrow-derived MSCs. In both cases the percentages of CD14+ cells were increased in co-cultures of MSCs and DCs and at the same time down-regulated the expression of CD80, CD86 and CD83 as in all experiments the effect of adipose tissue MSCs was stronger. Similarly, the secretion of IL-10 by dendritic cells was up-regulated in co-cultures of MSCs and dendritic cells and the effect was stronger when adipose tissue-derived MSCs were used.Taken together all results presented reveal the higher potential of the adipose tissue-derived MSCs to inhibit the differentiation and expression of functionally important co-stimulatory molecules on the surface of monocyte-derived dendritic cells than the bone marrow-derived MSCs. 相似文献
88.
Sajad Hussain Syed Damien Goutte-Gattat Nils Becker Sam Meyer Manu Shubhdarshan Shukla Jeffrey J. Hayes Ralf Everaers Dimitar Angelov Jan Bednar Stefan Dimitrov 《Proceedings of the National Academy of Sciences of the United States of America》2010,107(21):9620-9625
Despite the key role of the linker histone H1 in chromatin structure and dynamics, its location and interactions with nucleosomal DNA have not been elucidated. In this work we have used a combination of electron cryomicroscopy, hydroxyl radical footprinting, and nanoscale modeling to analyze the structure of precisely positioned mono-, di-, and trinucleosomes containing physiologically assembled full-length histone H1 or truncated mutants of this protein. Single-base resolution •OH footprinting shows that the globular domain of histone H1 (GH1) interacts with the DNA minor groove located at the center of the nucleosome and contacts a 10-bp region of DNA localized symmetrically with respect to the nucleosomal dyad. In addition, GH1 interacts with and organizes about one helical turn of DNA in each linker region of the nucleosome. We also find that a seven amino acid residue region (121–127) in the COOH terminus of histone H1 was required for the formation of the stem structure of the linker DNA. A molecular model on the basis of these data and coarse-grain DNA mechanics provides novel insights on how the different domains of H1 interact with the nucleosome and predicts a specific H1-mediated stem structure within linker DNA. 相似文献
89.
Kremlev SG Gaurnier-Hausser AL Del Valle L Perez-Liz G Dimitrov S Tuszynski G 《Journal of neuroimmunology》2008,194(1-2):132-142
Angiocidin was originally identified as a potent inhibitor of angiogenesis and tumor growth in vivo. In addition to its involvement in the regulation of carcinogenesis, recent studies indicate that angiocidin may also play a significant role in immune system modulation. This report describes the expression and potential function of angiocidin in multiple sclerosis (MS), a severe demyelinating, inflammatory and autoimmune disease of the central nervous system (CNS). We demonstrated that angiocidin and interleukin-7 (IL-7) are over-expressed in brain lesions of MS patients. Angiocidin-treated monocytes, peripheral blood T cells and primary astrocytes secreted various cytokines and chemokines including, IL-6, IL-7, GM-CSF, and MCP-1. Addition of recombinant angiocidin to cell cultures was able to promote differentiation of monocytes into a macrophage-like cell, induce MHC class I and class II gene expression and activate CD4(+) and CD8(+) T lymphocytes. Consistent with these findings, angiocidin induced mononuclear phagocyte migration and adhesion as well as increased the IL-2 response by antigen-specific T cells to myelin basic protein peptide presented to them by autologous mononuclear phagocytes. Furthermore, we examined STAT3 expression in angiocidin stimulated mononuclear phagocytes, T cells, and primary astrocytes. We found that angiocidin markedly stimulates STAT3 expression in these cell populations. Angiocidin, therefore appears to play a previously unappreciated and potentially important role in the regulation of immune response during the clinical course of MS. 相似文献
90.
Bustamante M Hasler U Leroy V de Seigneux S Dimitrov M Mordasini D Rousselot M Martin PY Féraille E 《Journal of the American Society of Nephrology : JASN》2008,19(1):109-116
Recent evidence suggests that arginine vasopressin (AVP)-dependent aquaporin-2 expression is modulated by the extracellular calcium-sensing receptor (CaSR) in principal cells of the collecting duct, but the signaling pathways mediating this effect are unknown. Using a mouse cortical collecting duct cell line (mpkCCD(cl4)), we found that increasing the concentration of apical extracellular calcium or treating with the CaSR agonists neomycin or Gd(3+) attenuated AVP-dependent accumulation of aquaporin-2 mRNA and protein; CaSR gene-silencing prevented this effect. Calcium reduced the AVP-induced accumulation of cAMP, but this did not occur by increased degradation of cAMP by phosphodiesterases or by direct inhibition of adenylate cyclase. Notably, the effect of extracellular calcium on AVP-dependent aquaporin-2 expression was prevented by inhibition of calmodulin. In summary, our results show that high concentrations of extracellular calcium attenuate AVP-induced aquaporin-2 expression by activating the CaSR and reducing coupling efficiency between V(2) receptor and adenylate cyclase via a calmodulin-dependent mechanism in cultured cortical collecting duct cells. 相似文献