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71.
72.
The flowers of several families of seed plants warm themselves when they bloom. In some species, thermogenesis is regulated,
increasing the rate of respiration at lower ambient temperature (T
a) to maintain a somewhat stable floral temperature (T
f). The precision of this regulation is usually measured by plotting T
f over T
a. However, such measurements are influenced by environmental conditions, including wind speed, humidity, radiation, etc. This
study eliminates environmental effects by experimentally ‘clamping’ T
f at constant, selected levels and then measuring stabilized respiration rate. Regulating flowers show decreasing respiration
with rising T
f (Q
10 < 1). Q
10 therefore becomes a measure of the biochemical ‘precision’ of temperature regulation: lower Q
10 values indicate greater sensitivity of respiration to T
f and a narrower range of regulated temperatures. At the lower end of the regulated range, respiration is maximal, and further
decreases in floral temperature cause heat production to diminish. Below a certain tissue temperature (‘switching temperature’),
heat loss always exceeds heat production, so thermoregulation becomes impossible. This study compared three species of thermoregulatory
flowers with distinct values of precision and switching temperature. Precision was highest in Nelumbo nucifera (Q
10 = 0.16) moderate in Symplocarpus renifolius (Q
10 = 0.48) and low in Dracunculus vulgaris (Q
10 = 0.74). Switching temperatures were approximately 30, 15 and 20°C, respectively. There were no relationships between precision,
switching temperature or maximum respiration rate. High precision reveals a powerful inhibitory mechanism that overwhelms
the tendency of temperature to increase respiration. Variability in the shape and position of the respiration–temperature
curves must be accounted for in any explanation of the control of respiration in thermoregulatory flowers. 相似文献
73.
Barbara Chiavarina Diana Whitaker-Menezes Gemma Migneco Ubaldo E Martinez-Outschoorn Stephanos Pavlides Anthony Howell Herbert B Tanowitz Mathew C Casimiro Chenguang Wang Richard G Pestell Philip Grieshaber Jaime Caro Federica Sotgia Michael P Lisanti 《Cell cycle (Georgetown, Tex.)》2010,9(17):3534-3551
Our recent studies have mechanistically implicated a loss of stromal Cav-1 expression and HIF1α-activation in driving the cancer-associated fibroblast phenotype, through the paracrine production of nutrients via autophagy and aerobic glycolysis. However, it remains unknown if HIF1α-activation is sufficient to confer the cancer-associated fibroblast phenotype. To test this hypothesis directly, we stably-expressed activated HIF1α in fibroblasts and then examined their ability to promote tumor growth using a xenograft model employing human breast cancer cells (MDA-MB-231). Fibroblasts harboring activated HIF1α showed a dramatic reduction in Cav-1 levels and a shift towards aerobic glycolysis, as evidenced by a loss of mitochondrial activity, and an increase in lactate production. Activated HIF1α also induced BNIP3 and BNIP3L expression, markers for the autophagic destruction of mitochondria. Most importantly, fibroblasts expressing activated HIF1α increased tumor mass by ∼2-fold and tumor volume by ∼3-fold, without a significant increase in tumor angiogenesis. In this context, HIF1α also induced an increase in the lymph node metastasis of cancer cells. Similar results were obtained by driving NFκB activation in fibroblasts, another inducer of autophagy. Thus, activated HIF1α is sufficient to functionally confer the cancer-associated fibroblast phenotype. It is also known that HIF1α expression is required for the induction of autophagy in cancer cells. As such, we next directly expressed activated HIF1α in MDA-MB-231 cells and assessed its effect on tumor growth via xenograft analysis. Surprisingly, activated HIF1α in cancer cells dramatically suppressed tumor growth, resulting in a 2-fold reduction in tumor mass and a three-fold reduction in tumor volume. We conclude that HIF1α activation in different cell types can either promote or repress tumorigenesis. Based on these studies, we suggest that autophagy in cancer-associated fibroblasts promotes tumor growth via the paracrine production of recycled nutrients, which can directly “feed” cancer cells. Conversely, autophagy in cancer cells represses tumor growth via their “self-digestion.” Thus, we should consider that the activities of various known oncogenes and tumor-suppressors may be compartment and cell-type specific, and are not necessarily an intrinsic property of the molecule itself. As such, other “classic” oncogenes and tumor suppressors will have to be re-evaluated to determine their compartment specific effects on tumor growth and metastasis. Lastly, our results provide direct experimental support for the recently proposed “autophagic tumor stroma model of cancer.”Key words: caveolin-1, autophagy, mitophagy, the Warburg effect, tumor stroma, hypoxia, HIF1A, NFκB, compartment-specific oncogenesis, cancer-associated fibroblasts 相似文献
74.
Ana Rodríguez-Campello Jordi Jiménez-Conde ángel Ois Elisa Cuadrado-Godia Eva Giralt-Steinhauer Helmut Schroeder Gemma Romeral Mireia Llop Carolina Soriano-Tárraga Montserrat Garralda-Anaya Jaume Roquer 《PloS one》2014,9(12)
Background and Aims
Diet appears to have some role in stroke development. The objective of our study was to describe the dietary habits in patients admitted with acute ischemic stroke and compare selected dietary components with healthy controls. Adherence to healthy diet behaviors was also assessed.Methods
A case-control study of consecutive patients with acute ischemic stroke admitted to the Neurology Department of Hospital del Mar from 2007 to 2010. Patients were matched by age and sex with control subjects. A previously validated nutritional survey was administered to patients and controls. Demographic data, vascular risk factors, caloric intake and dietary nutrients were evaluated. Intention to follow a healthy diet was also assessed in both groups.Results
A total of 300 acute ischemic stroke patients and 300 controls with evaluation of dietary habits. No differences were observed in vascular risk factors, except smoking habit, diabetes and ischemic heart disease. Stroke patients reported a higher caloric intake: 2444.8(1736.8–3244.5) vs 2208.7(1753.1–2860.7) Kcal, p = 0.001. After adjusting for energy intake, patients had higher intake of proteins (p<0.001; OR 1.02), total cholesterol (p = 0.001; OR 1.04), and breaded foods (p = 0.001; OR 1.94) and lower consumption of probiotic yogurt (p = 0.002; OR 0.88). Compared to patients, control participants indicated greater intention to eat vegetables (p = 0.002; OR 1.5) and whole foods (p = 0.000; OR 2.4) and reduce their intake of salt (p = 0.002; OR 1.7), fat (p = 0.000; OR 3.7) and sweets (p = 0.004; OR 1.7) than patients.Conclusion
We observed different dietary patterns between stroke patients and controls. Stroke patients have a higher caloric intake and are less concerned about maintaining healthy nutritional habits. 相似文献75.
Alberto L'Abbate Gemma Macchia Pietro D'Addabbo Angelo Lonoce Doron Tolomeo Domenico Trombetta Klaas Kok Christoph Bartenhagen Christopher W. Whelan Orazio Palumbo Marco Severgnini Ingrid Cifola Martin Dugas Massimo Carella Gianluca De Bellis Mariano Rocchi Lucia Carbone Clelia Tiziana Storlazzi 《Nucleic acids research》2014,42(14):9131-9145
The mechanism for generating double minutes chromosomes (dmin) and homogeneously staining regions (hsr) in cancer is still poorly understood. Through an integrated approach combining next-generation sequencing, single nucleotide polymorphism array, fluorescent in situ hybridization and polymerase chain reaction-based techniques, we inferred the fine structure of MYC-containing dmin/hsr amplicons harboring sequences from several different chromosomes in seven tumor cell lines, and characterized an unprecedented number of hsr insertion sites. Local chromosome shattering involving a single-step catastrophic event (chromothripsis) was recently proposed to explain clustered chromosomal rearrangements and genomic amplifications in cancer. Our bioinformatics analyses based on the listed criteria to define chromothripsis led us to exclude it as the driving force underlying amplicon genesis in our samples. Instead, the finding of coexisting heterogeneous amplicons, differing in their complexity and chromosome content, in cell lines derived from the same tumor indicated the occurrence of a multi-step evolutionary process in the genesis of dmin/hsr. Our integrated approach allowed us to gather a complete view of the complex chromosome rearrangements occurring within MYC amplicons, suggesting that more than one model may be invoked to explain the origin of dmin/hsr in cancer. Finally, we identified PVT1 as a target of fusion events, confirming its role as breakpoint hotspot in MYC amplification. 相似文献
76.
77.
Rebecca Kozor Stuart M. Grieve Stefan Buchholz Sharlene Kaye Shane Darke Ravinay Bhindi Gemma A. Figtree 《PloS one》2014,9(4)
Background
The cardiovascular impact of cocaine use in otherwise healthy individuals who consider themselves ‘social’ users is not well established.Methods/Results
Twenty regular cocaine users and 20 control subjects were recruited by word-of-mouth. Cardiovascular magnetic resonance was performed to assess cardiac and vascular structure and function. Cocaine users had higher systolic blood pressure compared to non-users (134±11 vs 126±11 mmHg, p = 0.036), a finding independent of age, body surface area, smoking and alcohol consumption. Cocaine use was associated with increased arterial stiffness - reflected by reduced aortic compliance (1.3±0.2 vs 1.7±0.5 cm2×10−2.mmHg−1, p = 0.004), decreased distensibility (3.8±0.9 vs 5.1±1.4 mmHg−1.10−3, p = 0.001), increased stiffness index (2.6±0.6 vs 2.1±0.6, p = 0.005), and higher pulse wave velocity (5.1±0.6 vs 4.4±0.6 m.s−1, p = 0.001). This change in aortic stiffness was independent of vessel wall thickness. Left ventricular mass was 18% higher in cocaine users (124±25 vs 105±16 g, p = 0.01), a finding that was independent of body surface area, and left atrial diameter was larger in the user group than controls (3.8±0.6 vs 3.5±0.3 cm, p = 0.04). The increased left ventricular mass, systolic blood pressure and vascular stiffness measures were all associated with duration and/or frequency of cocaine use. No late gadolinium enhancement or segmental wall motion abnormalities were seen in any of the subjects.Conclusions
Compared with the non-user control cohort, cocaine users had increased aortic stiffness and systolic blood pressure, associated with greater left ventricular mass. These measures are all well known risk factors for premature cardiovascular events, highlighting the dangers of cocaine use, even in a ‘social’ setting, and have important public health implications. 相似文献78.
Davies SJ Ayscough AP Beckett RP Bragg RA Clements JM Doel S Grew C Launchbury SB Perkins GM Pratt LM Smith HK Spavold ZM Thomas SW Todd RS Whittaker M 《Bioorganic & medicinal chemistry letters》2003,13(16):2709-2713
Structural modifications to the peptide deformylase inhibitor BB-3497 are described. In this paper, we describe the initial SAR around this lead for modifications to the methylene spacer and the P1' side chain. Enzyme inhibition and antibacterial activity data revealed that the optimum distance between the N-formyl hydroxylamine metal binding group and the P1' side chain is one unsubstituted methylene unit. Additionally, lipophilic P1' side chains that closely mimic the methionine residue in the substrate provided compounds with the best microbiological profile. 相似文献
79.
Neus Calbet‐Llopart Mirella Pascini‐Garrigos Gemma Tell‐Martí Miriam Potrony Vanessa Martins da Silva Alicia Barreiro Susana Puig Guillaume Captier Isabelle James Nathalie Degardin Cristina Carrera Josep Malvehy Heather C. Etchevers Joan Anton Puig‐Butill 《Pigment cell & melanoma research》2020,33(5):685-694
Congenital melanocytic nevi (CMN) are cutaneous malformations whose prevalence is inversely correlated with projected adult size. CMN are caused by somatic mutations, but epidemiological studies suggest that germline genetic factors may influence CMN development. In CMN patients from the U.K., genetic variants in MC1R, such as p.V92M and loss‐of‐function variants, have been previously associated with larger CMN. We analyzed the association of MC1R variants with CMN characteristics in two distinct cohorts of medium‐to‐giant CMN patients from Spain (N = 113) and from France, Norway, Canada, and the United States (N = 53), similar at the clinical and phenotypical level except for the number of nevi per patient. We found that the p.V92M or loss‐of‐function MC1R variants either alone or in combination did not correlate with CMN size, in contrast to the U.K. CMN patients. An additional case–control analysis with 259 unaffected Spanish individuals showed a higher frequency of MC1R compound heterozygous or homozygous variant genotypes in Spanish CMN patients compared to the control population (15.9% vs. 9.3%; p = .075). Altogether, this study suggests that MC1R variants are not associated with CMN size in these non‐UK cohorts. Additional studies are required to define the potential role of MC1R as a risk factor in CMN development. 相似文献
80.
Izquierdo-Useros N Lorizate M Contreras FX Rodriguez-Plata MT Glass B Erkizia I Prado JG Casas J Fabriàs G Kräusslich HG Martinez-Picado J 《PLoS biology》2012,10(4):e1001315
HIV-1 is internalized into mature dendritic cells (mDCs) via an as yet undefined mechanism with subsequent transfer of stored, infectious virus to CD4+ T lymphocytes. Thus, HIV-1 subverts a DC antigen capture mechanism to promote viral spread. Here, we show that gangliosides in the HIV-1 membrane are the key molecules for mDC uptake. HIV-1 virus-like particles and liposomes mimicking the HIV-1 lipid composition were shown to use a common internalization pathway and the same trafficking route within mDCs. Hence, these results demonstrate that gangliosides can act as viral attachment factors, in addition to their well known function as cellular receptors for certain viruses. Furthermore, the sialyllactose molecule present in specific gangliosides was identified as the determinant moiety for mDC HIV-1 uptake. Thus, sialyllactose represents a novel molecular recognition pattern for mDC capture, and may be crucial both for antigen presentation leading to immunity against pathogens and for succumbing to subversion by HIV-1. 相似文献