全文获取类型
收费全文 | 2099篇 |
免费 | 132篇 |
国内免费 | 9篇 |
专业分类
2240篇 |
出版年
2017年 | 20篇 |
2016年 | 18篇 |
2015年 | 46篇 |
2014年 | 64篇 |
2013年 | 90篇 |
2012年 | 121篇 |
2011年 | 102篇 |
2010年 | 63篇 |
2009年 | 61篇 |
2008年 | 86篇 |
2007年 | 62篇 |
2006年 | 78篇 |
2005年 | 72篇 |
2004年 | 70篇 |
2003年 | 72篇 |
2002年 | 64篇 |
2001年 | 81篇 |
2000年 | 66篇 |
1999年 | 65篇 |
1998年 | 22篇 |
1997年 | 24篇 |
1996年 | 25篇 |
1995年 | 24篇 |
1994年 | 32篇 |
1993年 | 21篇 |
1992年 | 46篇 |
1991年 | 45篇 |
1990年 | 38篇 |
1989年 | 31篇 |
1988年 | 35篇 |
1987年 | 24篇 |
1986年 | 19篇 |
1985年 | 40篇 |
1984年 | 26篇 |
1983年 | 27篇 |
1980年 | 15篇 |
1979年 | 22篇 |
1978年 | 25篇 |
1977年 | 15篇 |
1975年 | 15篇 |
1974年 | 19篇 |
1973年 | 13篇 |
1971年 | 19篇 |
1958年 | 23篇 |
1957年 | 26篇 |
1956年 | 26篇 |
1955年 | 22篇 |
1954年 | 22篇 |
1953年 | 13篇 |
1952年 | 13篇 |
排序方式: 共有2240条查询结果,搜索用时 15 毫秒
991.
992.
Although semi-natural grasslands in Europe are declining there is often a time delay in the local extinction of grassland species due to development of remnant populations, i.e., populations with an extended persistence despite a negative growth rate. The objectives of this study were to examine the occurrence of remnant populations after abandonment of semi-natural grasslands and to examine functional traits of plants associated with the development of remnant populations. We surveyed six managed semi-natural grasslands and 20 former semi-natural grasslands where management ceased 60–100 years ago, and assessed species response to abandonment, assuming a space-for-time substitution. The response of species was related to nine traits representing life cycle, clonality, leaf traits, seed dispersal and seed mass. Of the 67 species for which data allowed analysis, 44 species declined after grassland abandonment but still occurred at the sites, probably as remnant populations. Five traits were associated with the response to abandonment. The declining but still occurring species were characterized by high plant height, a perennial life form, possession of a perennial bud bank, high clonal ability, and lack of dispersal attributes promoting long-distance dispersal. Traits allowing plants to maintain populations by utilizing only a part of their life cycle, such as clonal propagation, are most important for the capacity to develop remnant populations and delay local extinction. A considerable fraction of the species inhabiting semi-natural grasslands maintain what is most likely remnant populations after more than 60 years of spontaneous succession from managed semi-natural grasslands to forest. 相似文献
993.
Zhai G Teumer A Stolk L Perry JR Vandenput L Coviello AD Koster A Bell JT Bhasin S Eriksson J Eriksson A Ernst F Ferrucci L Frayling TM Glass D Grundberg E Haring R Hedman AK Hofman A Kiel DP Kroemer HK Liu Y Lunetta KL Maggio M Lorentzon M Mangino M Melzer D Miljkovic I;MuTHER Consortium Nica A Penninx BW Vasan RS Rivadeneira F Small KS Soranzo N Uitterlinden AG Völzke H Wilson SG Xi L Zhuang WV Harris TB Murabito JM Ohlsson C Murray A de Jong FH Spector TD Wallaschofski H 《PLoS genetics》2011,7(4):e1002025
Dehydroepiandrosterone sulphate (DHEAS) is the most abundant circulating steroid secreted by adrenal glands--yet its function is unknown. Its serum concentration declines significantly with increasing age, which has led to speculation that a relative DHEAS deficiency may contribute to the development of common age-related diseases or diminished longevity. We conducted a meta-analysis of genome-wide association data with 14,846 individuals and identified eight independent common SNPs associated with serum DHEAS concentrations. Genes at or near the identified loci include ZKSCAN5 (rs11761528; p = 3.15 × 10(-36)), SULT2A1 (rs2637125; p = 2.61 × 10(-19)), ARPC1A (rs740160; p = 1.56 × 10(-16)), TRIM4 (rs17277546; p = 4.50 × 10(-11)), BMF (rs7181230; p = 5.44 × 10(-11)), HHEX (rs2497306; p = 4.64 × 10(-9)), BCL2L11 (rs6738028; p = 1.72 × 10(-8)), and CYP2C9 (rs2185570; p = 2.29 × 10(-8)). These genes are associated with type 2 diabetes, lymphoma, actin filament assembly, drug and xenobiotic metabolism, and zinc finger proteins. Several SNPs were associated with changes in gene expression levels, and the related genes are connected to biological pathways linking DHEAS with ageing. This study provides much needed insight into the function of DHEAS. 相似文献
994.
Thelin J Jörntell H Psouni E Garwicz M Schouenborg J Danielsen N Linsmeier CE 《PloS one》2011,6(1):e16267
The function of chronic brain machine interfaces depends on stable electrical contact between neurons and electrodes. A key step in the development of interfaces is therefore to identify implant configurations that minimize adverse long-term tissue reactions. To this end, we here characterized the separate and combined effects of implant size and fixation mode at 6 and 12 weeks post implantation in rat (n = 24) cerebral cortex. Neurons and activated microglia and astrocytes were visualized using NeuN, ED1 and GFAP immunofluorescence microscopy, respectively. The contributions of individual experimental variables to the tissue response were quantified. Implants tethered to the skull caused larger tissue reactions than un-tethered implants. Small diameter (50 µm) implants elicited smaller tissue reactions and resulted in the survival of larger numbers of neurons than did large diameter (200 µm) implants. In addition, tethering resulted in an oval-shaped cavity, with a cross-section area larger than that of the implant itself, and in marked changes in morphology and organization of neurons in the region closest to the tissue interface. Most importantly, for implants that were both large diameter and tethered, glia activation was still ongoing 12 weeks after implantation, as indicated by an increase in GFAP staining between week 6 and 12, while this pattern was not observed for un-tethered, small diameter implants. Our findings therefore clearly indicate that the combined small diameter, un-tethered implants cause the smallest tissue reactions. 相似文献
995.
Background
Extensive DNA damage leads to apoptosis. Histones play a central role in DNA damage sensing and may mediate signals of genotoxic damage to cytosolic effectors including mitochondria.Methodology/Principal Findings
We have investigated the effects of histones on mitochondrial function and membrane integrity. We demonstrate that both linker histone H1 and core histones H2A, H2B, H3, and H4 bind strongly to isolated mitochondria. All histones caused a rapid and massive release of the pro-apoptotic intermembrane space proteins cytochrome c and Smac/Diablo, indicating that they permeabilize the outer mitochondrial membrane. In addition, linker histone H1, but not core histones, permeabilized the inner membrane with a collapse of the membrane potential, release of pyridine nucleotides, and mitochondrial fragmentation.Conclusions
We conclude that histones destabilize the mitochondrial membranes, a mechanism that may convey genotoxic signals to mitochondria and promote apoptosis following DNA damage. 相似文献996.
Hypothyroidism is the most common thyroid disorder, affecting about 5% of the general population. Here we present the current largest genome-wide association study of hypothyroidism, in 3,736 cases and 35,546 controls. Hypothyroidism was assessed via web-based questionnaires. We identify five genome-wide significant associations, three of which are well known to be involved in a large spectrum of autoimmune diseases: rs6679677 near PTPN22, rs3184504 in SH2B3, and rs2517532 in the HLA class I region (p-values 2.8·10(-13), 2.6·10(-12), and 1.3·10(-8), respectively). We also report associations with rs4915077 near VAV3 (p-value 7.5·10(-10)) and rs925489 near FOXE1 (p value 2.4·10(-19)). VAV3 is involved in immune function, and FOXE1 and PTPN22 have previously been associated with hypothyroidism. Although the HLA class I region and SH2B3 have previously been linked with a number of autoimmune diseases, this is the first report of their association with thyroid disease. The VAV3 association is also novel. We also show suggestive evidence of association for hypothyroidism with a SNP in the HLA class II region (independent of the other HLA association) as well as SNPs in CAPZB, PDE8B, and CTLA4. CAPZB and PDE8B have been linked to TSH levels and CTLA4 to a variety of autoimmune diseases. These results suggest heterogeneity in the genetic etiology of hypothyroidism, implicating genes involved in both autoimmune disorders and thyroid function. Using a genetic risk profile score based on the top association from each of the five genome-wide significant regions in our study, the relative risk between the highest and lowest deciles of genetic risk is 2.0. 相似文献
997.
998.
Edmund J Kayombo Febronia C Uiso Rogasian LA Mahunnah 《Journal of ethnobiology and ethnomedicine》2012,8(1):1-8
Health care utilization in many developing countries, Tanzania included, is mainly through the use of traditional medicine (TRM) and its practitioners despite the presence of the conventional medicine. This article presents findings on the study that aimed to get an experience of health care utilization from both urban and rural areas of seven administrative regions in Tanzania. A total of 33 health facility managers were interviewed on health care provision and availability of supplies including drugs, in their respective areas. The findings revealed that the health facilities were overburden with higher population to serve than it was planned. Consequently essential drugs and other health supplies were available only in the first two weeks of the month. Conventional health practitioners considered traditional health practitioners to be more competent in mental health management, and overall, they were considered to handle more HIV/AIDS cases knowingly or unknowingly due to shear need of healthcare by this group. In general conventional health practitioners were positive towards traditional medicine utilization; and some of them admitted using traditional medicines. Traditional medicines like other medical health systems worldwide have side effects and some contentious ethical issues that need serious consideration and policy direction. Since many people will continue using traditional/alternative medicine, there is an urgent need to collaborate with traditional/alternative health practitioners through the institutionalization of basic training including hygiene in order to improved healthcare in the community and attain the Millennium Development Goals by 2015. 相似文献
999.
Medetomidine is a new antifouling substance, highly effective against barnacles. As part of a thorough ecotoxicological evaluation of medetomidine, its short-term effects on algal and bacterial communities were investigated and environmental concentrations were predicted with the MAMPEC model. Photosynthesis and bacterial protein synthesis for three marine communities, viz. periphyton, epipsammon and plankton were used as effect indicators, and compared with the predicted environmental concentrations (PECs). The plankton community showed a significant decrease in photosynthetic activity of 16% at 2 mg l?1 of medetomidine, which was the only significant effect observed. PECs were estimated for a harbor, shipping lane and marina environment using three different model scenarios (MAMPEC default, Baltic and OECD scenarios). The highest PEC of 57 ng l?1, generated for a marina with the Baltic scenario, was at least 10,000-fold lower than the concentration that significantly decreased photosynthetic activity. It is concluded that medetomidine does not cause any acute toxic effects on bacterial protein synthesis and only small acute effects on photosynthesis at high concentrations in marine microbial communities. It is also concluded that the hazard from medetomidine on these processes is low since the effect levels are much lower than the highest PEC. 相似文献
1000.
Palma M Hansson L Choudhury A Näsman-Glaser B Eriksson I Adamson L Rossmann E Widén K Horváth R Kokhaei P Vertuani S Mellstedt H Osterborg A 《Cancer immunology, immunotherapy : CII》2012,61(6):865-879
We previously demonstrated that autologous dendritic cells that have endocytosed apoptotic bodies of chronic lymphocytic leukemia (CLL) cells (Apo-DC) can stimulate antileukemic T cell responses in vitro. In this phase I study, we vaccinated 15 asymptomatic CLL patients at five time points with Apo-DC administered intradermally either alone (cohort I), or in combination with subcutaneous granulocyte-macrophage-colony-stimulating-factor (GM-CSF) (cohort II) or with GM-CSF and intravenous low-dose cyclophosphamide (cohort III). Aim of the study was to evaluate the safety and immunogenicity of Apo-DC alone or in combination with GM-CSF and low-dose cyclophosphamide in CLL patients. All patients completed the vaccination schedule without dose-limiting toxicity. No objective clinical responses were seen. Vaccine-induced leukemia-specific immune responses were evaluated by IFN-γ ELISpot and proliferation assays over a 52 weeks observation period and immune response criteria were defined. According to these criteria, 10/15 patients were defined as immune responders. The frequency of immune-responding patients was higher in cohorts II (3/5) and III (5/5) than in cohort I (2/5). In order to further characterize the induced immune response, estimation of secreted cytokines and CD107-degranulation assay were performed. Clustering of T and CLL cells was observed in CD107-degranulation assay and visualized by confocal microscopy. Additionally, assessment of regulatory T cells (T(regs)) revealed their significantly lower frequencies in immune responders versus non-responders (P?0.0001). Cyclophosphamide did not reduce T(regs) frequency. In conclusion, vaccination with Apo-DC + GM-CSF and cyclophosphamide was safe and elicited anti-CLL immune responses that correlated inversely with T(regs) levels. Lack of clinical responses highlights the necessity to develop more potent vaccine strategies in B cell malignancies. 相似文献