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   791篇
  免费   37篇
  2023年   3篇
  2022年   6篇
  2021年   8篇
  2020年   5篇
  2019年   3篇
  2018年   6篇
  2017年   11篇
  2016年   15篇
  2015年   29篇
  2014年   30篇
  2013年   54篇
  2012年   38篇
  2011年   51篇
  2010年   16篇
  2009年   27篇
  2008年   50篇
  2007年   53篇
  2006年   52篇
  2005年   53篇
  2004年   55篇
  2003年   39篇
  2002年   27篇
  2001年   7篇
  2000年   8篇
  1999年   7篇
  1998年   10篇
  1997年   11篇
  1996年   4篇
  1995年   9篇
  1994年   6篇
  1993年   6篇
  1992年   10篇
  1991年   12篇
  1990年   6篇
  1989年   5篇
  1988年   12篇
  1987年   6篇
  1986年   9篇
  1985年   3篇
  1984年   4篇
  1983年   5篇
  1982年   7篇
  1981年   9篇
  1980年   9篇
  1978年   4篇
  1976年   5篇
  1974年   6篇
  1973年   2篇
  1970年   3篇
  1966年   3篇
排序方式: 共有828条查询结果,搜索用时 15 毫秒
81.
The KCNQ1 gene encodes a voltage-dependent potassium ion channel, and mutations in this gene are the most common cause of congenital long QT syndrome (LQTS). In the present study, we investigated the various phenotypic characteristics of vertigo 2 Jackson (C3H/HeJCrl-Kcnq1(vtg-2J)/J) mice with a Kcnq1 mutation. Both heterozygotes (vtg-2J/+) and homozygotes (vtg-2J/vtg-2J) showed prolonged QT intervals in electrocardiograms (ECGs) compared to C3H/HeJ control (+/+) mice. Furthermore, vtg-2J/vtg-2J mice showed gastric achlorhydria associated with elevation of their serum gastrin levels. The serum corticosterone levels were also significantly increased in vtg-2J/vtg-2J mice. In addition, vtg-2J/vtg-2J mice exhibited significantly higher blood pressure. These findings indicate that the Kcnq1 mutation in vtg-2J mice alters various physiological functions in the cardiac, gastric and adrenocortical systems, and suggest that vtg-2J mice may represent a useful model for studying Kcnq1 functions.  相似文献   
82.
A significant number of patients are diagnosed with "fevers of unknown origin" (FUO) in Shimane Prefecture in Japan where tick-borne diseases are endemic. We conducted molecular surveys for Babesia microti, Ehrlichia species, and Candidatus Neoehrlichia mikurensis in 62 FUO cases and 62 wild rodents from Shimane Prefecture, Japan. PCR using primers specific for the Babesia 18S small-subunit rRNA (rDNA) gene and Anaplasmataceae groESL amplified products from 45% (28/62) and 25.8% (16/62) of captured mice, respectively. Of the 28 18S rDNA PCR positives, 23 and five samples were positive for Hobetsu- and Kobe-type B. microti, respectively. In contrast, of the 16 groESL PCR positives, eight, one and seven samples were positive for Ehrlichia muris, Ehrlichia sp. HF565 and Candidatus N. mikurensis, respectively. Inoculation of selected blood samples into Golden Syrian hamsters indicated the presence of Hobetsu- and Kobe-type B. microti in four and one sample, respectively. Isolation of the latter strain was considered important as previous studies suggested that the distribution of this type was so far confined to Awaji Island in Hyogo Prefecture, where the first case of transfusion-associated human babesiosis originated. DNA samples from 62 FUO human cases tested negative for B. microti 18S rDNA gene, Anaplasmataceae groESL gene, Rickettsia japonica 17K genus-common antigen gene and Orientia tsutsugamushi 56K antigen gene by PCRs. We also conducted seroepidemiological surveys on 62 human sera collected in Shimane Prefecture from the FUO patients who were suspected of carrying tick-borne diseases. However, indirect immunofluorescent antibody tests using B. microti- and E. muris-infected cells detected IgG against E. muris in only a single positive sample. This study demonstrates the presence of several potentially important tick-borne pathogens in Shimane Prefecture and suggests the need for further study on the causative agents of FUOs.  相似文献   
83.
To evaluate hypoxic cells in live mouse liver tissues, immunohistochemistry for protein adducts of reductively activated pimonidazole (PARaPi) was performed using the “in vivo cryotechnique (IVCT)” followed by freeze-substitution fixation. This method was used because cryotechniques have some merits for examining biological events in living animal organs with improved time-resolution compared to conventional perfusion and/or immersion chemical fixation. Pimonidazole was intraperitoneally injected into living mice, and then after various times of hypoxia, their livers were quickly frozen by IVCT. The frozen liver tissues were freeze-substituted in acetone containing 2% paraformaldehyde, and routinely embedded in paraffin wax. De-paraffinized sections were immunostained for PARaPi. In liver tissues of mice without hypoxia, almost no immunostained cells were detected. However, in liver tissues with 30 s of hypoxia, some hepatocytes in the pericentral zones were strongly immunostained. After 60 s of hypoxia, many hepatocytes were immunostained with various degrees of staining intensity in all lobular zones, indicating different reactivities of pimonidazole in the hepatocytes to hypoxia. At this time, the general immunoreactivity also appeared to be stronger around the central veins than other portal areas. Although many hepatocytes were immunostained for PARaPi in the liver tissues with perfusion fixation via heart, those with perfusion via portal vein were not immunostained. Thus, IVCT is useful to detect time-dependent hypoxic states with pimonidazole treatment in living animal organs.  相似文献   
84.
Cicuta virosa L. plants can grow in a pond subjected to heavy‐metal inputs at the Hitachi mine, eastern Japan. They accumulate heavy‐metal elements, especially high concentrations of zinc (Zn), in their roots. We focused on the role that root bacterial endophytes play in the heavy‐metal uptake of plants and the provision of heavy‐metal tolerance within plants. Our purpose was to clarify the effects of endophytes on: (i) Zn accumulation in C. virosa roots; (ii) growth of C. virosa seedlings; and (iii) heavy‐metal tolerance of C. virosa plants. Root endophytic Pseudomonas putida and Rhodopseudomonas sp., which induced the high production of Zn‐chelating compounds, were selected for the seedling inoculation test. The results of the inoculation test demonstrated that both strains of endophytes increased Zn accumulation in C. virosa roots by solubilizing Zn in the sediment. Both strains also increased the growth of seedlings by possible production of indole‐3‐acetic acid in the plant. The heavy‐metal tolerance of C. virosa seedlings was likely promoted by producing metal‐chelating compounds that detoxify the metals in the plant tissues, and by decreasing the heavy‐metal contents in the tissues via rapid seedling growth. Thus, such mutualistic interactions between plants and bacteria contribute to the persistence of C. virosa in this severe environment.  相似文献   
85.
86.
The coconut hispine beetle, Brontispa longissima, is a serious invasive pest of coconut palm (Cocos nucifera) in Southeast Asia and the Pacific region. Recently, however, it has been reported that on Ishigaki Island, Japan, where C. nucifera is rare, the endemic palm Satakentia liukiuensis serves as a regular host. To explore this phenomenon, we examined the preferences of the beetle for the two palm hosts by choice tests and measurements of feeding amount using four different groups: naïve adults obtained from a colony reared on C. nucifera (NC); naïve adults from a colony reared on S. liukiuensis (NS); wild adults collected on C. nucifera on Ishigaki Island (WC); and wild adults collected on S. liukiuensis on Ishigaki Island (WS). Both NC and NS consumed significantly more C. nucifera leaves than S. liukiuensis leaves and were observed more often on the leaves of C. nucifera. These results suggest that B. longissima has an innate preference for C. nucifera. In contrast, field‐collected adults (WC, WS) initially showed preferences for the species on which they were collected, but after exposure to the other host plant for 2 weeks, their preferences for that host increased. These results suggest that the feeding experience of B. longissima adults affected their subsequent host preferences. This flexible host preference may have facilitated the beetle’s successful establishment in novel Japanese habitats where the original host plant was rare.  相似文献   
87.
88.

Background

The objective of the present study was to determine whether the morbidity rates of the 2009 pandemic influenza A H1N1 virus (pdmH1N1) varied by age and/or sex.

Methods and Findings

Retrospective analysis of 2,024,367 cases of pdmH1N1 was performed using the national surveillance data from influenza sentinel points in Japan. The male-to-female morbidity ratios (M/F ratios) in nineteen age groups were estimated as the primary outcome. The M/F ratios for pdmH1N1 influenza were: >1 in age groups <20 years and ≥80 years (p<0.001); <1 in age groups 20–79 years (p<0.001). This data suggests that males <20 years of age may be more likely to suffer from pdmH1N1 influenza than females in the same age categories. When the infection pattern for pdmH1N1was compared with that of seasonal influenza outbreaks between 2000 and 2008, the M/F ratio for pdmH1N1 influenza was higher in ages 3–29 years and lower in ages 40–79 years. Because the present study was based on the national surveillance, it was impossible to estimate the morbidity rate for the Japanese population. It is also likely that the data did not capture asymptomatic or mild infections.

Conclusions

Although exposure to the pdmH1N1 virus is assumed to be similar in both boys and girls, M/F ratios were >1 in those younger than 20 years. The subsequent reversal of the M/F ratio in the adult generation could be due to several possibilities, including: greater immunity among adult males, more asymptomatic infections among males, less reporting of illness by males, or differences in exposure to the virus and probability of visiting a clinic. These results suggest that the infection and virulence patterns of pdmH1N1 are more complex than previously considered.  相似文献   
89.
The extremely thermostable NAD-dependent glutamate dehydrogenase (NAD-GluDH) from Pyrobaculum islandicum, a member of the Crenarchaeota, was crystallized, and its 3D structure has been determined by X-ray diffraction methods. The homohexameric structure of Pb. islandicum glutamate dehydrogenase (Pis-GluDH) was solved and refined at a resolution of 2.9A with a crystallographic R-factor of 19.9% (Rfree 26.0%). The structure indicates that each subunit consists of two domains separated by a deep cleft containing an active site. The secondary structural elements and catalytically important residues of the enzyme were highly conserved among the NAD(P)-dependent GluDHs from other sources. A structural comparison of Pis-GluDH with other NAD(P)-dependent GluDHs suggests that a significant difference in the alpha8-loop-alpha9 region of this enzyme is associated with its coenzyme specificity. From the analysis of the 3D structure, hydrophobic interactions between intersubunits were found to be important features for the enzyme oligomerization. It has been reported that Pis-GluDH is highly thermostable, like the GluDH of the hyperthermophilic archaeum Pyrococcus furiosus, and the increase in the intersubunit ion pair networks is responsible for the extreme thermostability of the Pc. furiosus enzyme. However, the number of intersubunit ion pairs in the Pis-GluDH molecules is much smaller than those of the Pc. furiosus GluDH. The number of hydrophobic interactions at the intersubunit interfaces were increased and responsible for the extremely high thermostability. This indicates that the major molecular strategy for high thermostability of the GluDHs may be different for each hyperthermophile.  相似文献   
90.
Protein 4.1 families have recently been established as potential organizers of an adherens system. In the adult mouse testis, protein 4.1G (4.1G) localized as a line pattern in both basal and adluminal compartments of the seminiferous tubules, attaching regions of germ cells and Sertoli cells. By double staining for 4.1G and F-actin, their localizations were shown to be different, indicating that 4.1G was localized in a region other than the basal and apical ectoplasmic specializations, which formed the Sertoli–Sertoli cell junction and Sertoli–spermatid junction, respectively. By electron microscopy, immunoreactive products were seen exclusively on the cell membranes of Sertoli cells, attaching to the various differentiating germ cells. The immunolocalization of cadherin was identical to that of 4.1G, supporting the idea that 4.1G may be functionally interconnected with adhesion molecules. In an experimental mouse model of cadmium treatment, in which tight and adherens junctions of seminiferous tubules were disrupted, the 4.1G immunostaining in the seminiferous tubules was dramatically decreased. These results indicate that 4.1G may have a basic adhesive function between Sertoli cells and germ cells from the side of Sertoli cells.  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