全文获取类型
收费全文 | 561篇 |
免费 | 26篇 |
国内免费 | 1篇 |
出版年
2023年 | 7篇 |
2022年 | 12篇 |
2021年 | 14篇 |
2020年 | 5篇 |
2019年 | 11篇 |
2018年 | 10篇 |
2017年 | 9篇 |
2016年 | 15篇 |
2015年 | 23篇 |
2014年 | 32篇 |
2013年 | 27篇 |
2012年 | 35篇 |
2011年 | 36篇 |
2010年 | 25篇 |
2009年 | 16篇 |
2008年 | 33篇 |
2007年 | 32篇 |
2006年 | 25篇 |
2005年 | 23篇 |
2004年 | 19篇 |
2003年 | 36篇 |
2002年 | 24篇 |
2001年 | 8篇 |
2000年 | 10篇 |
1999年 | 7篇 |
1998年 | 4篇 |
1997年 | 10篇 |
1996年 | 4篇 |
1995年 | 3篇 |
1994年 | 3篇 |
1993年 | 7篇 |
1992年 | 2篇 |
1990年 | 2篇 |
1989年 | 3篇 |
1988年 | 3篇 |
1986年 | 2篇 |
1984年 | 3篇 |
1983年 | 2篇 |
1981年 | 3篇 |
1979年 | 4篇 |
1978年 | 3篇 |
1977年 | 6篇 |
1975年 | 3篇 |
1974年 | 3篇 |
1973年 | 5篇 |
1972年 | 2篇 |
1968年 | 3篇 |
1962年 | 2篇 |
1933年 | 1篇 |
1930年 | 1篇 |
排序方式: 共有588条查询结果,搜索用时 20 毫秒
101.
The dissociation of casein was studied after addition of polyphosphate that leads to calcium chelation, using light and X-ray scattering and turbidimetry. It is shown that the dissociation is a cooperative process; that is, a casein complex is either completely dissociated or remains largely intact. A systematic study was done of the dependence of the rate and extent of dissociation on the polyphosphate concentration and was found to be determined by the ratio between casein and polyphosphate. The structures of the casein complex and the small micellar particles formed after dissociation were compared. Additional experiments with a different chelatant (EDTA) gave similar results. 相似文献
102.
Redlich G Zanger UM Riedmaier S Bache N Giessing AB Eisenacher M Stephan C Meyer HE Jensen ON Marcus K 《Journal of proteome research》2008,7(11):4678-4688
In mammals, Cytochrome P450 (CYP) enzymes are bound to membranes of the endoplasmic reticulum and mitochondria, where they are responsible for the oxidative metabolism of many xenobiotics as well as organic endogenous compounds. In humans, 57 isoforms were identified which are classified based on sequence homology. In the present work, we demonstrate the performance of a mass spectrometry-based strategy to simultaneously detect and differentiate distinct human Cytochrome P450 (CYP) isoforms including the highly similar CYP3A4, CYP3A5, CYP3A7, as well as CYP2C8, CYP2C9, CYP2C18, CYP2C19, and CYP4F2, CYP4F3, CYP4F11, CYP4F12. Compared to commonly used immunodetection methods, mass spectrometry overcomes limitations such as low antibody specificity and offers high multiplexing possibilities. Furthermore, CYP phosphorylation, which may affect various biochemical and enzymatic properties of these enzymes, is still poorly analyzed, especially in human tissues. Using titanium dioxide resin combined with tandem mass spectrometry for phosphopeptide enrichment and sequencing, we discovered eight human P450 phosphorylation sites, seven of which were novel. The data from surgical human liver samples establish that the isoforms CYP1A2, CYP2A6, CYP2B6, CYP2E1, CYP2C8, CYP2D6, CYP3A4, CYP3A7, and CYP8B1 are phosphorylated in vivo. These results will aid in further investigation of the functional significance of protein phosphorylation for this important group of enzymes. 相似文献
103.
104.
The treatment of facial paralysis is generally considered to have been nonsurgical until the end of the nineteenth century. However, the authors discovered recently that already in the 1840s the celebrated German facial reconstructive surgeons Dieffenbach and von Langenbeck applied the technique of subcutaneous myotomy to healthy facial muscles to reestablish balance in the chronically paralyzed faces of their patients. They performed their operations at a time when anesthesia, asepsis, antisepsis, and antibiotics had not yet been introduced into surgery. It is concluded that Dieffenbach and von Langenbeck were the first, in recorded history, to develop a surgical way to treat irreversible facial paralysis. As their principles are still being used in surgical practice, they cannot be regarded as antiquated, which illustrates the difficulties that reconstructive surgeons still experience in the treatment of irreversible facial paralysis. 相似文献
105.
Octávio Mateus Susannah C.R. Maidment Nicolai A. Christiansen 《Proceedings. Biological sciences / The Royal Society》2009,276(1663):1815-1821
Stegosaurian dinosaurs have a quadrupedal stance, short forelimbs, short necks, and are generally considered to be low browsers. A new stegosaur, Miragaia longicollum gen. et sp. nov., from the Late Jurassic of Portugal, has a neck comprising at least 17 cervical vertebrae. This is eight additional cervical vertebrae when compared with the ancestral condition seen in basal ornithischians such as Scutellosaurus. Miragaia has a higher cervical count than most of the iconically long-necked sauropod dinosaurs. Long neck length has been achieved by ‘cervicalization’ of anterior dorsal vertebrae and probable lengthening of centra. All these anatomical features are evolutionarily convergent with those exhibited in the necks of sauropod dinosaurs. Miragaia longicollum is based upon a partial articulated skeleton, and includes the only known cranial remains from any European stegosaur. A well-resolved phylogeny supports a new clade that unites Miragaia and Dacentrurus as the sister group to Stegosaurus; this new topology challenges the common view of Dacentrurus as a basal stegosaur. 相似文献
106.
Fungal entomopathogens are often studied within the context of their use for biological control, yet these natural enemies are also excellent subjects for studies of ecological interactions. Here, we present selected principles from community ecology and discuss these in relation to fungal entomopathogens. We discuss the relevance of apparent competition, food web construction, intraguild predation and density-mediated and trait-mediated indirect effects. Although current knowledge of community interactions involving fungal entomopathogens are limited, fungal entomopathogens can be important, interactive members of communities and the activities of fungal entomopathogens should be evaluated in the context of ecological principles. We also discuss aspects of metapopulation ecology and the application of these principles to fungal entomopathogens. Knowledge of ecological interactions is crucial if we are to understand and predict the effects of fungal entomopathogens on host populations and understand the interactions among fungal entomopathogens and other organisms in the communities in which they occur. 相似文献
107.
Li C Allen A Kwagh J Doliba NM Qin W Najafi H Collins HW Matschinsky FM Stanley CA Smith TJ 《The Journal of biological chemistry》2006,281(15):10214-10221
Insulin secretion by pancreatic beta-cells is stimulated by glucose, amino acids, and other metabolic fuels. Glutamate dehydrogenase (GDH) has been shown to play a regulatory role in this process. The importance of GDH was underscored by features of hyperinsulinemia/hyperammonemia syndrome, where a dominant mutation causes the loss of inhibition by GTP and ATP. Here we report the effects of green tea polyphenols on GDH and insulin secretion. Of the four compounds tested, epigallocatechin gallate (EGCG) and epicatechin gallate were found to inhibit GDH with nanomolar ED(50) values and were therefore found to be as potent as the physiologically important inhibitor GTP. Furthermore, we have demonstrated that EGCG inhibits BCH-stimulated insulin secretion, a process that is mediated by GDH, under conditions where GDH is no longer inhibited by high energy metabolites. EGCG does not affect glucose-stimulated insulin secretion under high energy conditions where GDH is probably fully inhibited. We have further shown that these compounds act in an allosteric manner independent of their antioxidant activity and that the beta-cell stimulatory effects are directly correlated with glutamine oxidation. These results demonstrate that EGCG, much like the activator of GDH (BCH), can facilitate dissecting the complex regulation of insulin secretion by pharmacologically modulating the effects of GDH. 相似文献
108.
Li Q Eklund AC Juul N Haibe-Kains B Workman CT Richardson AL Szallasi Z Swanton C 《PloS one》2010,5(12):e15031
Background
Expression of the oestrogen receptor (ER) in breast cancer predicts benefit from endocrine therapy. Minimising the frequency of false negative ER status classification is essential to identify all patients with ER positive breast cancers who should be offered endocrine therapies in order to improve clinical outcome. In routine oncological practice ER status is determined by semi-quantitative methods such as immunohistochemistry (IHC) or other immunoassays in which the ER expression level is compared to an empirical threshold[1], [2]. The clinical relevance of gene expression-based ER subtypes as compared to IHC-based determination has not been systematically evaluated. Here we attempt to reduce the frequency of false negative ER status classification using two gene expression approaches and compare these methods to IHC based ER status in terms of predictive and prognostic concordance with clinical outcome.Methodology/Principal Findings
Firstly, ER status was discriminated by fitting the bimodal expression of ESR1 to a mixed Gaussian model. The discriminative power of ESR1 suggested bimodal expression as an efficient way to stratify breast cancer; therefore we identified a set of genes whose expression was both strongly bimodal, mimicking ESR expression status, and highly expressed in breast epithelial cell lines, to derive a 23-gene ER expression signature-based classifier. We assessed our classifiers in seven published breast cancer cohorts by comparing the gene expression-based ER status to IHC-based ER status as a predictor of clinical outcome in both untreated and tamoxifen treated cohorts. In untreated breast cancer cohorts, the 23 gene signature-based ER status provided significantly improved prognostic power compared to IHC-based ER status (P = 0.006). In tamoxifen-treated cohorts, the 23 gene ER expression signature predicted clinical outcome (HR = 2.20, P = 0.00035). These complementary ER signature-based strategies estimated that between 15.1% and 21.8% patients of IHC-based negative ER status would be classified with ER positive breast cancer.Conclusion/Significance
Expression-based ER status classification may complement IHC to minimise false negative ER status classification and optimise patient stratification for endocrine therapies. 相似文献109.
110.
Metadel K. Abera Pieter Verboven Thijs Defraeye Solomon Workneh Fanta Maarten L. A. T. M. Hertog Jan Carmeliet Bart M. Nicolai 《Annals of botany》2014,114(4):605-617