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71.
72.
Physicochemical Characterization of a Thermostable Alcohol Dehydrogenase from Pyrobaculum aerophilum
Annalisa Vitale Natasha Thorne Scott Lovell Kevin P. Battaile Xin Hu Min Shen Sabato D'Auria Douglas S. Auld 《PloS one》2013,8(6)
In this work we characterize an alcohol dehydrogenase (ADH) from the hyperthermophilic archaeon Pyrobaculum aerophilum (PyAeADHII). We have previously found that PyAeADHII has no activity when standard ADH substrates are used but is active when α-tetralone is used as substrate. Here, to gain insights into enzyme function, we screened several chemical libraries for enzymatic modulators using an assay employing α-tetralone. The results indicate that PyAeADHII activity in the presence of α-tetralone was inhibited by compounds such as flunarizine. We also examined metal coordination of the enzyme in solution by performing metal substitution of the enzyme-bound zinc (Zn2+) with cobalt. The solution-based absorption spectra for cobalt substituted PyAeADHII supports substitution at the structural Zn2+ site. To gain structural insight, we obtained the crystal structure of both wild-type and cobalt-substituted PyAeADHII at 1.75 Å and 2.20 Å resolution, respectively. The X-ray data confirmed one metal ion per monomer present only at the structural site with otherwise close conservation to other ADH enzymes. We next determined the co-crystal structure of the NADPH-bound form of the enzyme at 2.35 Å resolution to help define the active site region of the enzyme and this data shows close structural conservation with horse ADH, despite the lack of a catalytic Zn2+ ion in PyAeADHII. Modeling of α-tetralone into the NADPH bound structure suggests an arginine as a possible catalytic residue. The data presented here can yield a better understanding of alcohol dehydrogenases lacking the catalytic zinc as well as the structural features inherent to thermostable enzymes. 相似文献
73.
Bennett PC Cooper N Rohlf VI Mornement K 《Journal of applied animal welfare science : JAAWS》2007,10(3):217-241
The aim of this study was to survey people currently attending companion-dog-training facilities about their reasons for attending training, their expectations prior to training, their training experiences, and the factors contributing to their satisfaction with these experiences. The 178 participants indicated that they experienced few canine behavioral difficulties prior to attending training, with factors other than dog behavior influencing their decision to attend a particular facility. Features identified as important were characteristics of the instructors and the facility itself, opportunities for the dog caretaker (owner) to develop dog-training skills and knowledge, and specific canine behavior outcomes. Satisfaction was a multidimensional concept: satisfaction with the instructors and facility being dissociable from satisfaction with progress made by the dog and handler. Each of these represented different aspects of the training experience. Training facilities may need to address a wide range of issues to engage additional dog owners in training activities. Identification of these issues is an important first step in this process. 相似文献
74.
Sprouty2 binds Grb2 at two different proline-rich regions, and the mechanism of ERK inhibition is independent of this interaction 总被引:2,自引:0,他引:2
Martínez N García-Domínguez CA Domingo B Oliva JL Zarich N Sánchez A Gutiérrez-Eisman S Llopis J Rojas JM 《Cellular signalling》2007,19(11):2277-2285
Sprouty2 has been widely implicated in the negative regulation of the fibroblast growth factor receptor-extracellular regulated kinase (ERK) pathway. Sprouty2 directly interacts with the adapter protein Grb2, member of the receptor tyrosine kinase-induced signaling pathways. In considering the functional role of Grb2, we investigated whether the interaction with this protein was responsible for ERK pathway inhibition. We found that the binding between Sprouty2 and Grb2 is constitutive, independent of Sprouty2 tyrosine phosphorylation, although it is increased when fibroblast growth factor receptor is activated. This connection is mediated by the N-terminal SH3 domain of Grb2 and two Sprouty2 proline-rich stretches (residues 59-64 and 303-307). Most importantly, a double Sprouty2 mutant (hSpry2 P59AP304A), which is unable to bind Grb2, developed at a similar inhibition level of fibroblast growth factor receptor-ERK pathway than that which originated from Sprouty2 wt. These results are evidence that the Sprouty2 mechanism of ERK inhibition is independent of Grb2 binding. 相似文献
75.
Carly Griffin Natasha Sharda Divya Sood Jerald Nair James McNulty Siyaram Pandey 《Cancer cell international》2007,7(1):10
Background
Pancratistatin (PST), a compound extracted from an Amaryllidaceae (AMD) family plant, has been shown to specifically induce apoptosis in cancer cells with no/minimal toxic effect on normal cells. A systematic synthetic approach has indicated that the minimum cytotoxic pharmacophore comprises the trans-fused b/c-ring system containing the 2, 3, 4-triol unit in the C-ring. To further explore the structure-activity relationship of this group of compounds we have investigated the anti-cancer efficacy and specificity of two PST-related natural compounds, AMD4 and AMD5. Both of these compounds lack the polyhydroxylated lycorane element of PST instead having a methoxy-substuituted crinane skeleton. 相似文献76.
Theories of sexual and natural selection predict coevolution of visual perception with conspecific colour and/or the light environment animals occupy. One way to test these theories is to focus on the visual system, which can be achieved by studying the opsin-based visual pigments that mediate vision. Birds vary greatly in colour, but opsin gene coding sequences and associated visual pigment spectral sensitivities are known to be rather invariant across birds. Here, I studied expression of the four cone opsin genes (Lws, Rh2, Sws2 and Sws1) in 16 species of New World warblers (Parulidae). I found levels of opsin expression vary both across species and between the sexes. Across species, female, but not male Sws2 expression is associated with an index of sexual selection, plumage dichromatism. This fits predictions of classic sexual selection models, in which the sensory system changes in females, presumably impacting female preference, and co-evolves with male plumage. Expression of the opsins at the extremes of the light spectrum, Lws and Uvs, correlates with the inferred light environment occupied by the different species. Unlike opsin spectral tuning, regulation of opsin gene expression allows for fast adaptive evolution of the visual system in response to natural and sexual selection, and in particular, sex-specific selection pressures. 相似文献
77.
Natasha Musrap Alessandra Tuccitto George S. Karagiannis Punit Saraon Ihor Batruch Eleftherios P. Diamandis 《The Journal of biological chemistry》2015,290(28):17218-17227
Ovarian cancer is a lethal gynecological disease that is characterized by peritoneal metastasis and increased resistance to conventional chemotherapies. This increased resistance and the ability to spread is often attributed to the formation of multicellular aggregates or spheroids in the peritoneal cavity, which seed abdominal surfaces and organs. Given that the presence of metastatic implants is a predictor of poor survival, a better understanding of how spheroids form is critical to improving patient outcome, and may result in the identification of novel therapeutic targets. Thus, we attempted to gain insight into the proteomic changes that occur during anchorage-independent cancer cell aggregation. As such, an ovarian cancer cell line, OV-90, was cultured in adherent and non-adherent conditions using stable isotope labeling with amino acids in cell culture (SILAC). Anchorage-dependent cells (OV-90AD) were grown in tissue culture flasks, whereas anchorage-independent cells (OV-90AI) were grown in suspension using the hanging-drop method. Cellular proteins from both conditions were then identified using LC-MS/MS, which resulted in the quantification of 1533 proteins. Of these, 13 and 6 proteins were up-regulated and down-regulated, respectively, in aggregate-forming cells compared with cells grown as monolayers. Relative gene expression and protein expression of candidates were examined in other cell line models of aggregate formation (TOV-112D and ES-2), which revealed an increased expression of calcium-activated chloride channel regulator 1 (CLCA1). Moreover, inhibitor and siRNA transfection studies demonstrated an apparent effect of CLCA1 on cancer cell aggregation. Further elucidation of the role of CLCA1 in the pathogenesis of ovarian cancer is warranted. 相似文献
78.
79.
In 2009, the Royal Botanic Gardens, Kew (UK) launched its Breathing Planet Programme. This 10 year programme seeks to re-align
Kew’s work to develop plant-based solutions to the challenges of climate change. Further to the development of the Programme,
Kew has undertaken a review of its science projects with relevance to mitigating the impacts of climate change on plant diversity
and people. The review has allowed Kew to better understand its current strengths and weaknesses in this area in order to
plan for the future. The findings of the review could be relevant for science programmes in other botanic gardens. Botanic
gardens play a fundamental role in the conservation of biodiversity to mitigate climate change impacts. Knowledge and data
on plant systematics, distribution and physiology is vital for modelling and monitoring the impacts of climate change, to
help to identify plant species and habitats most at risk of losing their wild diversity. Kew’s Millennium Seed Bank Project
will safeguard 25% of plant species by 2020, while in situ projects are improving the conservation of threatened habitats.
One challenge is to make such activities relevant and useful to other scientists, conservation groups and policy makers working
to address climate change. However, botanic gardens must also develop working practices and projects that specifically address
the challenges of climate change. Kew and a global network of partners are doing this in a variety of ways, and examples will
be presented in this paper. 相似文献
80.
Mariarosaria Galeano Francesca Polito Alessandra Bitto Natasha IrreraGiuseppe M. Campo Angela AvenosoMargherita Calò Patrizia Lo CascioLetteria Minutoli Mauro BaroneFrancesco Squadrito Domenica Altavilla 《生物化学与生物物理学报:疾病的分子基础》2011,1812(7):752-759
Hyaluronic acid (HA), an essential component of the extracellular matrix, is an efficient space filler that maintains hydration, serves as a substrate for assembly of proteoglycans and is involved in wound healing. Although numerous pieces of evidence demonstrate beneficial effects in promoting wound healing in diabetes, a systemic approach has never been tested. We used an incisional wound healing model in genetically diabetic mice to test the effects of systemic injection of HA. Diabetic (n = 56) and normoglycemic (n = 56) mice were subjected to incision and randomized (8 groups of 7 animals each) to receive HA at different doses, 7.5, 15 and 30 mg/kg/i.p., or vehicle (0.9% NaCl solution) for 12 days. At the end of the experiment animals were sacrificed and skin wounds were excised for histological, biochemical and molecular analysis. Histology revealed that the most effective dose to improve wound repair and angiogenesis in diabetic mice was 30 mg/kg. Furthermore HA injection (30 mg/kg) improved the altered healing pattern in diabetic animals, increased skin remodeling proteins TGF-β and transglutaminase-II and restored the altered expression of cyclin B1/Cdc2 complex. Evaluation of skin from diabetic animals injected with HA revealed also an increase in HA content, suggesting that systemic injection may be able to restore the reduced intracellular HA pool of diabetic mice. Finally HA markedly improved skin mechanical properties. These promising results, if confirmed in a clinical setting, may improve the care and management of diabetic patients. 相似文献