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   1823篇
  免费   150篇
  1973篇
  2023年   3篇
  2022年   15篇
  2021年   26篇
  2020年   14篇
  2019年   15篇
  2018年   23篇
  2017年   21篇
  2016年   44篇
  2015年   73篇
  2014年   90篇
  2013年   98篇
  2012年   158篇
  2011年   147篇
  2010年   88篇
  2009年   96篇
  2008年   116篇
  2007年   131篇
  2006年   110篇
  2005年   117篇
  2004年   92篇
  2003年   100篇
  2002年   94篇
  2001年   27篇
  2000年   10篇
  1999年   24篇
  1998年   25篇
  1997年   24篇
  1996年   24篇
  1995年   27篇
  1994年   21篇
  1993年   18篇
  1992年   24篇
  1991年   8篇
  1990年   13篇
  1989年   6篇
  1988年   6篇
  1987年   5篇
  1986年   4篇
  1985年   3篇
  1984年   5篇
  1983年   4篇
  1979年   6篇
  1977年   1篇
  1973年   2篇
  1972年   2篇
  1969年   1篇
  1968年   4篇
  1966年   1篇
  1964年   3篇
  1957年   1篇
排序方式: 共有1973条查询结果,搜索用时 15 毫秒
41.
In this study, the role of Listeria monocytogenes ferritin was investigated. The fri gene encoding the ferritin was deleted and the phenotype of the mutant was analyzed demonstrating that ferritin is necessary for optimal growth in minimal medium in both presence and absence of iron, as well as after cold- and heat-shock. We also showed that ferritin provides protection against reactive oxygen species and is essential for full virulence of L. monocytogenes. A comparative proteomic analysis revealed an effect of the fri deletion on the levels of listeriolysin O and several stress proteins. Together, our study demonstrates that fri has multiple roles that contribute to Listeria virulence.  相似文献   
42.
43.
Although extensive evidence support the key role of adipokines in cartilage homeostasis, contradictory data have been found for their expression and their effects in chondrocytes. This study was then undertaken to determine whether a phenotypic modulation may affect the expression of adipokines and their receptors in human chondrocytes. The expression of leptin, adiponectin and their receptors, as well as cartilage-specific genes was examined in chondrocytes obtained from patients with osteoarthritis either directly after cells harvest or after culture in monolayer or in alginate beads. The results showed major changes in the gene expression pattern after culture in monolayer with a shift from the adipokines to their receptors. Interestingly, this downregulation of adipokines was associated with a loss of chondrocyte phenotype, and chondrocytes recovered a cartilage-like expression profile of leptin and adiponectin when cultured in a tridimensional chondrocyte phenotype-inducing system, but ceased expressing their receptors. Further experiments clearly showed that leptin but not adiponectin promoted the expression of cartilage-specific markers through mitogen-activated protein kinase, Janus kinase and phosphatidylinositol-3 kinase signaling pathways. In conclusion, our data indicate that any phenotypic modulation could affect chondrocyte responsiveness to leptin or adiponectin, and provide evidence for an important role for leptin in regulating the expression of cartilage-specific markers.  相似文献   
44.
Peroxiredoxins (Prxs) constitute a family of thiol peroxidases that reduce hydrogen peroxide, peroxinitrite, and hydroperoxides using a strictly conserved cysteine. Very abundant in all organisms, Prxs are produced as diverse isoforms characterized by different catalytic mechanisms and various thiol-containing reducing agents. The oligomeric state of Prxs and the link with their functionality is a subject of intensive research. We present here a combined X-ray and nuclear magnetic resonance (NMR) study of a plant Prx that belongs to the D-Prx (type II) subfamily. The Populus trichocarpa Prx is the first Prx shown to be regenerated in vitro by both the glutaredoxin and thioredoxin systems. The crystal structure and solution NMR provide evidence that the reduced protein is a specific noncovalent homodimer both in the crystal and in solution. The dimer interface is roughly perpendicular to the plane of the central beta sheet and differs from the interface of A- and B-Prx dimers, where proteins associate in the plane parallel to the beta sheet. The homodimer interface involves residues strongly conserved in the D (type II) Prxs, suggesting that all Prxs of this family can homodimerize. The study provides a new insight into the Prx oligomerism and the basis for protein-protein and enzyme-substrate interaction studies by NMR.  相似文献   
45.
An expressed sequence tag (EST) approach was used to retrieve cDNA clones involved in carbon metabolism in Laminaria digitata Lamouroux. Six partial open reading frames were identified, respectively encoding an α-type carbonic anhydrase (CA), glucose-6-phosphate dehydrogenase (G6PDH), 6-phosphogluconate dehydrogenase (6PGDH), phosphoglycerate kinase (PGK), glycolate oxidase (GLO), and GDP-4-keto-6-d-mannose-3,5-epimerase-4-reductase, also known as fucose synthase (FS). These enzymes were further characterized through Southern blot analyses, amino acid sequence comparisons, and patterns of expression. In contrast to the other genes, which are expressed in both the gametophytic and sporophytic generations of L. digitata, the α-type carbonic anhydrase messenger RNA was shown by RT-PCR and northern blot analyses to be present in the gametophytes only. The evolutionary relationships of these genes and their interest as molecular tools for investigating carbon fluxes in brown algae are discussed.  相似文献   
46.
47.
The impact of anthropogenic activity on ecosystems has highlighted the need to move beyond the biogeographical delineation of species richness patterns to understanding the vulnerability of species assemblages, including the functional components that are linked to the processes they support. We developed a decision theory framework to quantitatively assess the global taxonomic and functional vulnerability of fish assemblages on tropical reefs using a combination of sensitivity to species loss, exposure to threats and extent of protection. Fish assemblages with high taxonomic and functional sensitivity are often exposed to threats but are largely missed by the global network of marine protected areas. We found that areas of high species richness spatially mismatch areas of high taxonomic and functional vulnerability. Nevertheless, there is strong spatial match between taxonomic and functional vulnerabilities suggesting a potential win–win conservation‐ecosystem service strategy if more protection is set in these locations.  相似文献   
48.
Dynorphins, endogenous opioid peptides that arise from the precursor protein prodynorphin (Pdyn), are hypothesized to be involved in the regulation of mood states and the neuroplasticity associated with addiction. The current study tested the hypothesis that dynorphin in the nucleus accumbens (NAcc) mediates such effects. More specifically, we examined whether knockdown of Pdyn within the NAcc in rats would alter the expression of depressive-like and anxiety-like behavior, as well as cocaine locomotor sensitization. Wistar rats were injected with adeno-associated viral (AAV) vectors encoding either a Pdyn-specific short hairpin RNA (AAV-shPdyn) or a scrambled shRNA (AAV-shScr) as control. Four weeks later, rats were tested for anxiety-like behavior in the elevated plus maze test and depressive-like behavior in the forced swim test (FST). Finally, rats received one daily injection of saline or cocaine (20 mg/kg, i.p.), followed by assessment of locomotion for 4 consecutive days. Following 3 days of abstinence, the rats completed 2 additional daily cocaine/saline locomotor trials. Pdyn knockdown in the NAcc led to a significant reduction in depressive-like behavior in the FST, but had no effect on anxiety-like behavior in the elevated plus maze. Pdyn knockdown did not alter baseline locomotor behavior, the locomotor response to acute cocaine, or the initial sensitization of the locomotor response to cocaine over the first 4 cocaine treatment days. However, following 3 days abstinence the locomotor response to the cocaine challenge returned to their original levels in the AAV-shPdyn rats while remaining heightened in the AAV-shScr rats. These results suggest that dynorphin in a very specific area of the nucleus accumbens contributes to depressive-like states and may be involved in neuroadaptations in the NAcc that contribute to the development of cocaine addiction as a persistent and lasting condition.  相似文献   
49.
In mountain gorillas (Gorilla g. beringei), male immigration in bi-sexual units is rare. This paper presents the case of a nearly weaned male infant gorilla who followed his mother in her transfer. This case was recorded in the study population at the Kariske Research Center in 1988. The data come from observation in Group B (on 12 days just prior to the transfer and on 54 days after the transfer over a period of 6 months). The situation of the infant did match the conditions in which infanticide occurs in gorillas, but he was not killed, despite receiving male aggression and being wounded twice. In fact, both the mother and the infant received male aggression more frequently than the long term residents in the group. The aggression received by the mother decreased after she mated with the males and after she weaned the infant. The aggression received by the infant, however, did not decrease after his mother mated with the males, and increased in intensity. The infant reacted fearfully to male aggression, in marked contrast to his mother, who reacted either with indifference, or by simply avoiding the males. The aggression eventually stopped, and the infant became a blackback in Group B. Evolutionarily, the death of the infant would not have markedly accelerated the mother's return to estrus, but the death of the infant could still have benefitted the males, by decreasing the reproductive output of a competitor. Adult male gorillas are also presumably selected to resist male immigration. Proximately, the aggression directed towards the infant was not related to mating access to the mother. The sex of the infant may contribute to explain the post-transfer male aggression, but data on the integration of old female infants in a new group is needed to test whether the sex of the infant has an effect on their vulnerability to infanticide. Also, the intense fear displayed by the infant may have played a role in prompting male aggression.  相似文献   
50.
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