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   708篇
  免费   58篇
  2023年   6篇
  2022年   16篇
  2021年   22篇
  2020年   8篇
  2019年   11篇
  2018年   14篇
  2017年   17篇
  2016年   29篇
  2015年   40篇
  2014年   27篇
  2013年   50篇
  2012年   52篇
  2011年   51篇
  2010年   45篇
  2009年   31篇
  2008年   38篇
  2007年   46篇
  2006年   36篇
  2005年   21篇
  2004年   24篇
  2003年   32篇
  2002年   15篇
  2001年   11篇
  2000年   10篇
  1999年   10篇
  1998年   3篇
  1997年   5篇
  1996年   5篇
  1995年   3篇
  1994年   2篇
  1992年   3篇
  1991年   4篇
  1989年   5篇
  1988年   3篇
  1986年   3篇
  1985年   5篇
  1982年   2篇
  1980年   3篇
  1979年   4篇
  1978年   2篇
  1977年   2篇
  1976年   4篇
  1975年   15篇
  1974年   8篇
  1973年   4篇
  1971年   2篇
  1967年   4篇
  1966年   3篇
  1962年   1篇
  1944年   1篇
排序方式: 共有766条查询结果,搜索用时 15 毫秒
11.
Anthropological studies were done on 1276 Libyans from the Mediterranean cities of Tripoli and Benghazi, and from Sabha southward in The Sahara. The incidences of hemoglobin (Hb)-S and glucose-6-phosphate dehydrogenase (G-6-PD) deficiency were low in the coastal areas and significantly high in Sabha. Hb-C occurred sporadically in Tripoli and Sabha, and was absent from Benghazi in the east. One case of Hb-J Benghazi was noted. There were no significant differences in the ABO blood group and Rh0 (D) type distributions in the three localities. G-6-PD gene GdA frequency was significantly high in Sabha. The lowest value of 6-phosphogluconate dehydrogenase (6-PGD) gene PGDA frequency and highest value of the gene PGDC were in Sabha. Adenylate kinase (AK) gene AK2 was only detectable in Tripoli. Acid phosphatase (AP) gene Pa frequency in Sabha was more than twice that in Tripoli and Benghazi, while Pc was distinctly lower in Sabha than in the northern cities. Haptoglobin gene Hp1 frequency was almost identical in all areas. Anthropometric measurements revealed overall homogeneity of the three samples, closer similarity in the coastal region to adjacent North African populations, and Negroid influence in the Saharan Libyans. Anthropometry substantiated findings from blood markers.  相似文献   
12.
13.

Introduction

The aetiopathogenesis of juvenile dermatomyositis (JDM) remains poorly understood. In particular the contribution of monocytes or macrophages, which are frequently observed to be an infiltrate within muscle tissue very early in the disease process, is unknown. We hypothesised that these cells secrete the pro-inflammatory myeloid related protein (MRP) 8/14 which may then contribute to muscle pathology in JDM.

Methods

In this study of 56 JDM patients, serum MRP8/14 levels were compared with clinical measures of disease activity. Muscle biopsies taken early in disease were assessed by immunohistochemistry to determine the frequency and identity of MRP-expressing cells. The effects of MRP stimulation and endoplasmic reticulum (ER) stress on muscle were tested in vitro. Serum or supernatant levels of cytokines were analyzed by multiplex immunoassay.

Results

Serum MRP8/14 correlated with physician’s global assessment of disease activity in JDM (R = 0.65, p = 0.0003) and muscle strength/endurance, childhood myositis assessment score (CMAS, R = −0.55, p = 0.004). MRP8/14 was widely expressed by CD68+ macrophages in JDM muscle tissue. When cultured with human myoblasts, MRP8 led to the secretion of MCP-1 and IL-6, which was enhanced by ER stress. Both inflammatory mediators were detected in significantly higher levels in the serum of JDM patients compared to healthy controls.

Conclusions

This study is the first to identify serum MRP8/14 as a potential biomarker for disease activity in JDM. We propose that tissue infiltrating macrophages secreting MRP8/14 may contribute to myositis, by driving the local production of cytokines directly from muscle.  相似文献   
14.
15.
Large carnivores inhabiting ecosystems with heterogeneously distributed environmental resources with strong seasonal variations frequently employ opportunistic foraging strategies, often typified by seasonal switches in diet. In semi-arid ecosystems, herbivore distribution is generally more homogeneous in the wet season, when surface water is abundant, than in the dry season when only permanent sources remain. Here, we investigate the seasonal contribution of the different herbivore species, prey preference and distribution of kills (i.e. feeding locations) of African lions in Hwange National Park, Zimbabwe, a semi-arid African savanna structured by artificial waterholes. We used data from 245 kills and 74 faecal samples. Buffalo consistently emerged as the most frequently utilised prey in all seasons by both male (56%) and female (33%) lions, contributing the most to lion dietary biomass. Jacobs’ index also revealed that buffalo was the most intensively selected species throughout the year. For female lions, kudu and to a lesser extent the group “medium Bovidae” are the most important secondary prey. This study revealed seasonal patterns in secondary prey consumption by female lions partly based on prey ecology with browsers, such as giraffe and kudu, mainly consumed in the early dry season, and grazers, such as zebra and suids, contributing more to female diet in the late dry season. Further, it revealed the opportunistic hunting behaviour of lions for prey as diverse as elephants and mice, with elephants taken mostly as juveniles at the end of the dry season during droughts. Jacobs’ index finally revealed a very strong preference for kills within 2 km from a waterhole for all prey species, except small antelopes, in all seasons. This suggested that surface-water resources form passive traps and contribute to the structuring of lion foraging behaviour.  相似文献   
16.
Biomineralization in calcareous dinophytes (Thoracosphaeracaea, Peridiniales) takes place in coccoid cells and is presently poorly understood. Vacuolar crystal-like particles as well as collection sites within the prospective calcareous shell may play a crucial role during this process at the ultrastructural level. Using transmission electron microscopy, we investigated the ultrastructure of coccoid cells at an early developmental stage in fourteen calcareous dinophyte strains (corresponding to at least ten species of Calciodinellum, Calcigonellum, Leonella, Pernambugia, Scrippsiella, and Thoracosphaera). The shell of the coccoid cells consisted either of one (Leonella, Thoracosphaera) or two matrices (Scrippsiella and its relatives) of unknown element composition, whereas calcite is deposited in the only or the outer layer, respectively. We observed crystal-like particles in cytoplasmic vacuoles in cells of nine of the strains investigated and assume that they are widespread among calcareous dinophytes. However, similar structures are also found outside the Thoracosphaeraceae, and we postulate an evolutionarily old physiological pathway (possibly involved in detoxification) that later was specialized for calcification. We aim to contribute to a deeper knowledge of the biomineralization process in calcareous dinophytes.  相似文献   
17.
18.
The ability to establish genetic risk models is critical for early identification and optimal treatment of breast cancer. For such a model to gain clinical utility, more variants must be identified beyond those discovered in previous genome-wide association studies (GWAS). This is especially true for women at high risk because of family history, but without BRCA1/2 mutations. This study incorporates three datasets in a GWAS analysis of women with Ashkenazi Jewish (AJ) homogeneous ancestry. Two independent discovery cohorts comprised 239 and 238 AJ women with invasive breast cancer or preinvasive ductal carcinoma in situ and strong family histories of breast cancer, but lacking the three BRCA1/2 founder mutations, along with 294 and 230 AJ controls, respectively. An independent, third cohort of 203 AJ cases with familial breast cancer history and 263 healthy controls of AJ women was used for validation. A total of 19 SNPs were identified as associated with familial breast cancer risk in AJ women. Among these SNPs, 13 were identified from a panel of 109 discovery SNPs, including an FGFR2 haplotype. In addition, six previously identified breast cancer GWAS SNPs were confirmed in this population. Seven of the 19 markers were significant in a multivariate predictive model of familial breast cancer in AJ women, three novel SNPs [rs17663555(5q13.2), rs566164(6q21), and rs11075884(16q22.2)], the FGFR2 haplotype, and three previously published SNPs [rs13387042(2q35), rs2046210(ESR1), and rs3112612(TOX3)], yielding moderate predictive power with an area under the curve (AUC) of the ROC (receiver-operator characteristic curve) of 0.74. Population-specific genetic variants in addition to variants shared with populations of European ancestry may improve breast cancer risk prediction among AJ women from high-risk families without founder BRCA1/2 mutations.  相似文献   
19.
Individual bacterial cells can communicate via quorum sensing, cooperate to harvest nutrients from their environment, form multicellular biofilms, compete over resources and even kill one another. When the environment that bacteria inhabit is an animal host, these social behaviours mediate virulence. Over the last decade, much attention has focussed on the ecology, evolution and pathology of bacterial cooperation, and the possibility that it could be exploited or destabilised to treat infections. But how far can we really extrapolate from theoretical predictions and laboratory experiments to make inferences about ‘cooperative’ behaviours in hosts and reservoirs? To determine the likely importance and evolution of cooperation ‘in the wild’, several questions must be addressed. A recent paper that reports the dynamics of bacterial cooperation and virulence in a field experiment provides an excellent nucleus for bringing together key empirical and theoretical results which help us to frame – if not completely to answer – these questions.  相似文献   
20.
In this study, we have investigated inhibitory capacity of ethyl acetate, total oligomer flavonoid (TOF), aqueous extracts and beta amyrin acetate, a triterpene isolated from ethyl acetate extract obtained from leaves of Daphne gnidium, on mouse melanoma (B16-F0 and B16-F10 cells) proliferation. Influence of these products on percentage cell distribution in cycle phases and melanogenesis was also studied. Cell viability was determined using the 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, and flow cytometry was used to analyse effects of tested compounds on progression through the cell cycle. In addition, amounts of melanin and tyrosinase were measured spectrophotometrically at 475 nm. Ethyl acetate, TOF and aqueous extracts exhibited significant anti-proliferative activity after incubation with the two types of tumour skin cells B16-F0 and B16-F10. Furthermore, cell cycle analysis revealed that cells treated with ethyl acetate and TOF extracts were arrested predominantly in G2-M phase. Ethyl acetate extract has also the ability to enhance melanogenesis and tyrosinase activity of B16-F0 melanoma cells. Copyright © 2012 John Wiley & Sons, Ltd.  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