全文获取类型
收费全文 | 1684篇 |
免费 | 109篇 |
出版年
2023年 | 5篇 |
2022年 | 11篇 |
2021年 | 36篇 |
2020年 | 26篇 |
2019年 | 22篇 |
2018年 | 36篇 |
2017年 | 23篇 |
2016年 | 35篇 |
2015年 | 76篇 |
2014年 | 87篇 |
2013年 | 120篇 |
2012年 | 150篇 |
2011年 | 135篇 |
2010年 | 95篇 |
2009年 | 86篇 |
2008年 | 109篇 |
2007年 | 111篇 |
2006年 | 108篇 |
2005年 | 96篇 |
2004年 | 100篇 |
2003年 | 79篇 |
2002年 | 69篇 |
2001年 | 17篇 |
2000年 | 22篇 |
1999年 | 18篇 |
1998年 | 19篇 |
1997年 | 21篇 |
1996年 | 7篇 |
1995年 | 8篇 |
1994年 | 6篇 |
1993年 | 7篇 |
1992年 | 12篇 |
1991年 | 7篇 |
1990年 | 7篇 |
1989年 | 4篇 |
1988年 | 3篇 |
1987年 | 2篇 |
1986年 | 1篇 |
1985年 | 2篇 |
1984年 | 2篇 |
1983年 | 3篇 |
1982年 | 2篇 |
1980年 | 1篇 |
1979年 | 2篇 |
1978年 | 1篇 |
1974年 | 1篇 |
1972年 | 1篇 |
1970年 | 1篇 |
1957年 | 1篇 |
排序方式: 共有1793条查询结果,搜索用时 250 毫秒
1.
Glutamate is the main excitatory amino acid, but its presence in the extracellular milieu has deleterious consequences. It
may induce excitotoxicity and also compete with cystine for the use of the cystine–glutamate exchanger, blocking glutathione
neosynthesis and inducing an oxidative stress-induced cell death. Both mechanisms are critical in the brain where up to 20%
of total body oxygen consumption occurs. In normal conditions, the astrocytes ensure that extracellular concentration of glutamate
is kept in the micromolar range, thanks to their coexpression of high-affinity glutamate transporters (EAATs) and glutamine
synthetase (GS). Their protective function is nevertheless sensitive to situations such as oxidative stress or inflammatory
processes. On the other hand, macrophages and microglia do not express EAATs and GS in physiological conditions and are the
principal effector cells of brain inflammation. Since the late 1990s, a number of studies have now shown that both microglia
and macrophages display inducible EAAT and GS expression, but the precise significance of this still remains poorly understood.
Brain macrophages and microglia are sister cells but yet display differences. Both are highly sensitive to their microenvironment
and can perform a variety of functions that may oppose each other. However, in the very particular environment of the healthy
brain, they are maintained in a repressed state. The aim of this review is to present the current state of knowledge on brain
macrophages and microglial cells activation, in order to help clarify their role in the regulation of glutamate under pathological
conditions as well as its outcome. 相似文献
2.
Sandrine Reigadas Guerric Anies Bernard Masquelier Christina Calmels Lieven J. Stuyver Vincent Parissi Herve Fleury Marie-Line Andreola 《PloS one》2010,5(4)
Resistance to HIV-1 integrase (IN) inhibitor raltegravir (RAL), is encoded by mutations in the IN region of the pol gene. The emergence of the N155H mutation was replaced by a pattern including the Y143R/C/H mutations in three patients with anti-HIV treatment failure. Cloning analysis of the IN gene showed an independent selection of the mutations at loci 155 and 143. Characterization of the phenotypic evolution showed that the switch from N155H to Y143C/R was linked to an increase in resistance to RAL. Wild-type (WT) IN and IN with mutations Y143C or Y143R were assayed in vitro in 3′end-processing, strand transfer and concerted integration assays. Activities of mutants were moderately impaired for 3′end-processing and severely affected for strand transfer. Concerted integration assay demonstrated a decrease in mutant activities using an uncleaved substrate. With 3′end-processing assay, IC50 were 0.4 µM, 0.9 µM (FC = 2.25) and 1.2 µM (FC = 3) for WT, IN Y143C and IN Y143R, respectively. An FC of 2 was observed only for IN Y143R in the strand transfer assay. In concerted integration, integrases were less sensitive to RAL than in ST or 3′P but mutants were more resistant to RAL than WT. 相似文献
3.
Soil and climate are major constituents of the French notion of Terroir. This concept implies that there is a strong relationship
between the composition of the grape, the characteristics of the wine and the territory of production. To study this link,
a new method of characterization of the Terroir, including geological and pedological factors, was investigated. It uses a
field model based on depth and clay content of soil, together with the degree of weathering of the parent rock. Consequently,
for every type of parent rock belonging to a given geologic stage, there are a series of soils that show different stages
of pedological evolution. According to the model, three kinds of soils are distinguished with regards to the weathering intensity
of the parent rock, that are named weakly weathered rock (WWR), moderately weathered rock (MWR) and strongly weathered rock
(SWR). By hypothesis, each soil type is considered as a homogeneous unit for vine production from the viewpoint of ecophysiological
factors. Each terroir unit defined by this method is called a Basic Terroir Unit (BTU). To validate this hypothesis, experimental
plots planted with Chenin and Cabernet Franc vines were studied over three consecutive seasons (2000–2002), in the Anjou vineyard
(Loire Valley – France). The major BTUs developed on the two most important geological systems of Anjou (Brioverian and Ordovician–Devonian),
were studied. Results showed that the berries of vines cultivated in WWR were significantly smaller, richer in sugars and
anthocyanins and had a Total Phenolic Index higher than those of the vines cultivated in SWR. They also had a lower titratable
acidity. Cabernet Franc vines cultivated in MWR had berries with sugar and anthocyanin contents but also total phenolics very
close to those of WWR. With Chenin vines there was a good relationship between the global pool of free aromas of berries and
the BTU type. The study showed significant relationships between the quality of grapes and the measured values of several
ecophysiological variables such as the water supply regime or the timing of budburst. 相似文献
4.
5.
6.
Genetic heterogeneity in tuberous sclerosis 总被引:8,自引:0,他引:8
L A Janssen L A Sandkuyl E C Merkens J A Maat-Kievit J R Sampson P Fleury R C Hennekam G C Grosveld D Lindhout D J Halley 《Genomics》1990,8(2):237-242
Tuberous sclerosis (TSC) is an autosomal dominant disorder characterized by widespread hamartosis. Preliminary evidence of linkage between the TSC locus and markers on chromosome 9q34 was established, but subsequently disputed. More recently, a putative TSC locus on chromosome 11 has been suggested and genetic heterogeneity seems likely. Here we describe an approach combining multipoint linkage analysis and heterogeneity tests that has enabled us to obtain significant evidence for locus heterogeneity after studying a relatively small number of families. Our results support a model with two different loci independently causing the disease. One locus (TSC1) maps in the vicinity of the Abelson oncogene at 9q34 and a second locus (TSC2) maps in the region of the anonymous DNA marker Lam L7 and the dopamine D2 receptor gene at 11q23. 相似文献
7.
Marie-Hélène Avelange Jean M. Thiéry Frédéric Sarrey Pierre Gans Fabrice Rébeillé 《Planta》1991,183(2):150-157
In order to estimate photosynthetic and respiratory rates in illuminated photoautotrophic cells of carnation (Dianthus caryophyllus L.), simultaneous measurements of CO2 and O2 gas exchange were performed using 18O2, 13CO2 and a mass-spectrometry technique. This method allowed the determination, and thus the comparison, of unidirectional fluxes of O2 and CO2. In optimum photosynthetic conditions (i.e. in the presence of high light and a saturating level of CO2), the rate of CO2 influx represented 75±5% of the rate of gross O2 evolution. After a dark-to-light transition, the rate of CO2 efflux was inhibited by 50% whereas the O2-uptake rate was little affected. The effect of a recycling of respiratory CO2 through photosynthesis on the exchange of CO2 gas was investigated using a mathematical model. The confliction of the experimental data with the simulated gas-exchange rates strongly supported the view that CO2 recycling was a minor event in these cells and could not be responsible for the observed inhibition of CO2 efflux. On the basis of this assumption it was concluded that illumination of carnation cells resulted in a decrease of substrate decarboxylations, and that CO2 efflux and O2 uptake were not as tightly coupled in the light as in the dark. Furthermore, it could be calculated from the rate of gross photosynthesis that the chloroplastic electron-transport chain produced enough ATP in the light to account for the measured CO2-uptake rate without involving cyclic transfer of electrons around PS I or mitochondrial supplementation.Abbreviations Chl
chlorophyll
- Kd
permeability coefficient
The authors thank Drs A. Vermeglio and P. Thibault, Dépt. de Biologie, CEN-Cadarache, St. Paul Lez Durance, France, for helpful discussions. 相似文献
8.
Cell population obtained by bronchoalveolar lavage in Pneumocystis carinii pneumonitis 总被引:3,自引:0,他引:3
In the course of bronchoalveolar lavages performed in 115 immunocompromised patients in order to investigate the occurrences of pneumonitis, Pneumocystis carinii pneumonia was diagnosed by demonstration of cysts in bronchoalveolar lavage specimens from 11 patients. The cellular phenomena associated with P. carinii infection at the level of the alveolar space were evaluated. Differential cell counts on bronchoalveolar lavage preparations stained by the May-Grünwald-Giemsa method were performed in immunocompromised patients and in ten nonimmunocompromised patients without any respiratory disease. A decrease in the alveolar macrophage count associated with an increase in the polymorphonuclear neutrophil count and the presence of plasma cells and/or immunoblasts was highly suggestive of P. carinii pneumonia. These cellular changes in bronchoalveolar lavage specimens are discussed in relation to the pathologic features usually described in P. carinii pneumonia. 相似文献
9.
Jean-Jacques Fleury 《Geobios》1974,7(4):307-322
The formerly unknown microspheric form of Raadshoovenia salentina (Papetti and Tedeschi) and the new genus Cyclopseudedomia (type-species Cyclopseudedomia smouti n.g., n.sp.) are described from limestones of Campanian-Maastrichtian age from Gavrovo-Tripolitza zone in Greece. The new genus is distinguished from others of the sub-family RhapydionininaeKeijzer emend. Hamaoui and Fourcade by its almost entirely evolute test made of chambers tending to a cyclical stage (rapidly reached in the microspheric form). 相似文献
10.