全文获取类型
收费全文 | 1982篇 |
免费 | 126篇 |
国内免费 | 42篇 |
出版年
2021年 | 53篇 |
2020年 | 14篇 |
2019年 | 7篇 |
2018年 | 25篇 |
2017年 | 27篇 |
2016年 | 60篇 |
2015年 | 134篇 |
2014年 | 214篇 |
2013年 | 229篇 |
2012年 | 155篇 |
2011年 | 110篇 |
2010年 | 108篇 |
2009年 | 90篇 |
2008年 | 83篇 |
2007年 | 56篇 |
2006年 | 49篇 |
2005年 | 77篇 |
2004年 | 60篇 |
2003年 | 44篇 |
2002年 | 49篇 |
2001年 | 42篇 |
2000年 | 39篇 |
1999年 | 20篇 |
1998年 | 20篇 |
1997年 | 17篇 |
1996年 | 22篇 |
1995年 | 7篇 |
1993年 | 16篇 |
1992年 | 16篇 |
1991年 | 19篇 |
1990年 | 18篇 |
1989年 | 17篇 |
1988年 | 15篇 |
1987年 | 6篇 |
1986年 | 11篇 |
1985年 | 9篇 |
1983年 | 7篇 |
1982年 | 7篇 |
1981年 | 6篇 |
1979年 | 6篇 |
1978年 | 7篇 |
1974年 | 9篇 |
1973年 | 10篇 |
1972年 | 7篇 |
1971年 | 6篇 |
1968年 | 11篇 |
1965年 | 6篇 |
1962年 | 5篇 |
1957年 | 6篇 |
1951年 | 5篇 |
排序方式: 共有2150条查询结果,搜索用时 15 毫秒
101.
The isolation and characterization of multiple melatonin receptors in a wide range of tissues and cells signifies the functional diversity of melatonin. In different cellular environments, melatonin can regulate distinct second messengers or even positively or negatively regulate the same signal transduction pathway. The capacity by which melatonin receptors modulate the activities of various effector molecules is determined by the complement of signaling components present in any particular cell type. The specific interactions between many signaling molecules have been discerned in an increasing number of cellular systems and this information is being used to explain the physiological actions of melatonin. This review will attempt to summarize recent research by many groups that has revealed numerous subtleties of the melatonin-coupled signaling pathways. 相似文献
102.
103.
Olendzenski L Liu L Zhaxybayeva O Murphey R Shin DG Gogarten JP 《Journal of molecular evolution》2000,51(6):587-599
Members of the Deinococcaceae (e.g., Thermus, Meiothermus, Deinococcus) contain A/V-ATPases typically found in Archaea or Eukaryotes which were probably acquired by horizontal gene transfer. Two methods were used to quantify the extent to which archaeal or eukaryotic genes have been acquired by this lineage. Screening of a Meiothermus ruber library with probes made against Thermoplasma acidophilum DNA yielded a number of clones which hybridized more strongly than background. One of these contained the prolyl tRNA synthetase (RS) gene. Phylogenetic analysis shows the M. ruber and D. radiodurans prolyl RS to be more closely related to archaeal and eukaryal forms of this gene than to the typical bacterial type. Using a bioinformatics approach, putative open reading frames (ORFs) from the prerelease version of the D. radiodurans genome were screened for genes more closely related to archaeal or eukaryotic genes. Putative ORFs were searched against representative genomes from each of the three domains using automated BLAST. ORFs showing the highest matches against archaeal and eukaryotic genes were collected and ranked. Among the top-ranked hits were the A/V-ATPase catalytic and noncatalytic subunits and the prolyl RS genes. Using phylogenetic methods, ORFs were analyzed and trees assessed for evidence of horizontal gene transfer. Of the 45 genes examined, 20 showed topologies in which D. radiodurans homologues clearly group with eukaryotic or archaeal homologues, and 17 additional trees were found to show probable evidence of horizontal gene transfer. Compared to the total number of ORFs in the genome, those that can be identified as having been acquired from Archaea or Eukaryotes are relatively few (approximately 1%), suggesting that interdomain transfer is rare. 相似文献
104.
Abstract: Defective herpes simplex virus (HSV) vectors containing glutamic acid decarboxylase (GAD) cDNAs, either GAD65 or GAD67, were used to examine GAD function and GABA synthesis in rat cortical astrocytes, CNS cells that do not endogenously synthesize GABA. GAD vector infection resulted in isoform-specific expression of GAD as determined by western blotting and immunohistochemistry. Astrocytes infected with a β-galactosidase vector or uninfected expressed no GAD and contained no detectable GABA. GABA was detected in glial fibrillary acid protein-expressing cells after GAD65 vector infection. Significant amounts of GABA, as determined by HPLC, were synthesized in cultures infected with either GAD vector. The levels of GABA in GAD67 vector-infected cells were almost twofold higher than in GAD65 vector-infected cells. Vector infection did not alter levels of other intracellular amino acids. GABA was tonically released from astrocytes infected with the GAD67 vector, but no increase in release could be detected after treatment of the cells with K+ , veratridine, glutamate, or bradykinin. The ability to transduce astrocytes so that they express GAD and thereby increase GABA levels provides a potential strategy for the treatment of neurologic disorders associated with hyperexcitable or diminished inhibitory activity. 相似文献
105.
T. R. New 《Journal of Insect Conservation》2006,10(4):377-378
106.
Patrik Mráz Myriam Gaudeul Delphine Rioux Ludovic Gielly Philippe Choler Pierre Taberlet the IntraBioDiv Consortium 《Journal of Biogeography》2007,34(12):2100-2114
Aim The range of the subalpine species Hypochaeris uniflora covers the Alps, Carpathians and Sudetes Mountains. Whilst the genetic structure and post‐glacial history of many high‐mountain plant taxa of the Alps is relatively well documented, the Carpathian populations have often been neglected in phylogeographical studies. The aim of the present study is to compare the genetic variation of the species in two major European mountain systems – the Alps and the Carpathians. Location Alps and Carpathians. Methods The genetic variation of 77 populations, each consisting of three plants, was studied using amplified fragment length polymorphism (AFLP). Results Neighbour joining and principal coordinate analyses revealed three well‐supported phylogeographical groups of populations corresponding to three disjunct geographical regions – the Alps and the western and south‐eastern Carpathians. Moreover, two further clusters could be distinguished within the latter mountain range, one consisting of populations from the eastern Carpathians and the second consisting of populations from the southern Carpathians. Populations from the Apuseni Mountains had an intermediate position between the eastern and southern Carpathians. The genetic clustering of populations into four groups was also supported by an analysis of molecular variance, which showed that most genetic variation (almost 46%) was found among these four groups. By far the highest within‐population variation was found in the eastern Carpathians, followed by populations from the southern and western Carpathians. Generally, the populations from the Alps were considerably less variable and displayed substantially fewer region‐diagnostic markers than those from the south‐eastern Carpathians. Although no clear geographical structure was found within the Alps, based on neighbour joining or principal coordinate analyses, some trends were obvious: populations from the easternmost part were genetically more variable and, together with those from the south‐western part, exhibited a higher proportion of rare AFLP fragments than populations in other areas. Moreover, the total number of AFLP fragments per population, the percentage of polymorphic loci and the proportion of rare AFLP fragments significantly decreased from east to west. Main conclusions Deep infraspecific phylogeographical gaps between the populations from the Alps and the western and south‐eastern Carpathians suggest the survival of H. uniflora in three separate refugia during the last glaciation. Our AFLP data provide molecular evidence for a long‐term geographical disjunction between the eastern and western Carpathians, previously suggested from the floristic composition at the end of 19th century. It is likely that Alpine populations survived the Last Glacial in the eastern part of the Alps, from where they rapidly colonized the rest of the Alps after the ice sheet retreated. Multiple founder effects may explain a gradual loss of genetic variation during westward colonization of the Alps. 相似文献
107.
Alan Winston Rebekah Puls Stephen J. Kerr Chris Duncombe Patrick Li John M. Gill Reshmie Ramautarsing Simon D. Taylor-Robinson Sean Emery David A. Cooper for the ALTAIR Study Group 《PloS one》2015,10(2)
BackgroundChanges in cerebral metabolite ratios (CMR) measured on 1H-MRS and changes in cognitive function (CF) are described in subjects commencing combination antiretroviral therapy (cART), although the dynamics of such changes are poorly understood.MethodsNeuroasymptomatic, HIV-infected subjects electively commencing cART were eligible. CMR were assessed in three anatomical voxels and CF assessed at baseline, week 48 and week 144. Overall differences in absolute change in CMRs and CF parameters between 0–48 and 48–144 weeks were assessed.ResultsTwenty-two subjects completed study procedures. Plasma HIV-RNA was <50 copies/mL in all at week 48 and in all, but two subjects at week 144. In general, between weeks 0–48 a rise in N-acetyl-aspartate(NAA)/Creatine(Cr) ratio and a decline in myo-Inositol(mI)/Cr ratio were observed. Between weeks 48–144, small rises in NAA/Cr ratio were observed in two anatomical voxels, whereas a rise in mI/Cr ratio was observed in all anatomical locations (0.31 (0.66) and -0.27 (1.35) between weeks 0–48 and 0.13 (0.91) and 1.13 (1.71) between weeks 48–144 for absolute changes in NAA/Cr and mI/Cr (SD) in frontal-grey voxel, respectively). Global CF score improved between weeks 0–48 and then declined between weeks 48–144 (0.63 (1.16) and -0.63 (0.1.41) for mean absolute change (SD) between weeks 0–48 and weeks 48–144, respectively).ConclusionsThe direction of change of cerebral function parameters differs over time in HIV-infected subjects commencing cART, highlighting the need for long-term follow-up in such studies. The changes we have observed between weeks 48–144 may represent the initial development of cerebral toxicities from cART. 相似文献
108.
Li-Ting Ho Wei-Hsian Yin Shao-Yuan Chuang Wei-Kung Tseng Yen-Wen Wu I-Chang Hsieh Tsung-Hsien Lin Yi-Heng Li Lien-Chi Huang Kuo-Yang Wang Kwo-Chang Ueng Ching-Chang Fang Wen-Harn Pan Hung-I Yeh Chau-Chung Wu Jaw-Wen Chen Taiwanese Secondary Prevention for patients with AtheRosCLErotic disease Registry Investigators 《PloS one》2015,10(3)
Background
Epidemiological and clinical studies have clearly established the link between low-density lipoprotein cholesterol (LDL-C) and atherosclerosis-related cardiovascular consequences. Although it has been a common practice for physicians to prescribe lipid-lowering therapy for patients with dyslipidemia, the achievement rate is still not satisfied in Taiwan. Therefore, the determinants for achieving the LDL-C target needed to be clarified for better healthcare of the patients with dyslipidemia.Method
This registry-type prospective observational study enrolled the patients with cardiovascular diseases (coronary artery disease (CAD) and cerebrovascular disease (CVD)) from 18 medical centers across Taiwan, and clinically followed them for five years. At every clinical visit, vital signs, clinical endpoints, adverse events, concurrent medications and laboratory specimens were obtained as thoroughly as possible. The lipid profile (total cholesterol, high-density lipoprotein cholesterol, LDL-C, triglyceride), liver enzymes, and creatinine phosphokinase were evaluated at baseline, and every year thereafter. The cross sectional observational data was analyzed for this report.Result
Among the 3,486 registered patients, 54% had their LDL-C < 100 mg/dL. By univariate analysis, the patients achieving the LDL-C target were associated with older age, more male sex, taller height, lower blood pressure, more under lipid-lowering therapy, more smoking cessation, more history of CAD, DM, physical activity, but less history of CVD. The multivariate analysis showed statin therapy was the most significant independent determinant for achieving the treatment target, followed by age, history of CAD, diabetes, blood pressure, and sex. However, most patients were on regimens of very-low to low equipotent doses of statins.Conclusion
Although the lipid treatment guideline adherence is improving in recent years, only 54% of the patients with cardiovascular diseases have achieved their LDL-C target in Taiwan, and the most significant determinant for this was statin therapy. 相似文献109.
Elizabeth F. Closson Matthew J. Mimiaga Susan G. Sherman Arunrat Tangmunkongvorakul Ruth K. Friedman Mohammed Limbada Ayana T. Moore Kriengkrai Srithanaviboonchai Carla A. Alves Sarah Roberts Catherine E. Oldenburg Vanessa Elharrar Kenneth H. Mayer Steven A. Safren for the HPTN study team 《PloS one》2015,10(3)
110.
Marieke De Craemer Mina Lateva Violeta Iotova Ellen De Decker Ma?té Verloigne Ilse De Bourdeaudhuij Odysseas Androutsos Piotr Socha Zbigniew Kulaga Luis Moreno Berthold Koletzko Yannis Manios Greet Cardon the ToyBox-study group 《PloS one》2015,10(3)