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141.
Bossart GD Romano TA Peden-Adams MM Schaefer A McCulloch S Goldstein JD Rice CD Saliki JT Fair PA Reif JS 《Diseases of aquatic organisms》2011,97(2):103-112
Sera from free-ranging Atlantic bottlenose dolphins Tursiops truncatus inhabiting the Indian River Lagoon (IRL), Florida were tested for antibodies to cetacean morbilliviruses from 2003 to 2007 as part of a multidisciplinary study of individual and population health. A suite of clinicoimmunopathologic variables were evaluated in morbillivirus-seropositive dolphins (n = 14) and seronegative healthy dolphins (n = 49). Several important differences were found. Serum alkaline phosphatase, creatine phosphokinase, chloride, albumin and albumin/globulin ratios were significantly lower in seropositive dolphins. Innate immunity appeared to be upregulated with significant increases in lysozyme concentration and marginally significant increases in monocytic phagocytosis. Adaptive immunity was also impacted in dolphins with positive morbillivirus antibody titers. Mitogen-induced T lymphocyte proliferation responses were significantly reduced in dolphins with positive morbillivirus antibody titers, and marginally significant decreases were found for absolute numbers of CD4+ lymphocytes. The findings suggest impairment of cell-mediated adaptive immunity, similar to the immunologic pattern reported with acute morbillivirus infection in other species. In contrast, dolphins with positive morbillivirus antibody titers appeared to have at least a partially upregulated humoral immune response with significantly higher levels of gamma globulins than healthy dolphins, which may represent an antibody response to morbillivirus infection or other pathogens. These data suggest that subclinical dolphin morbillivirus infection in IRL dolphins may produce clinicoimmunopathologic perturbations that impact overall health. 相似文献
142.
Winter JN Jefferson LS Kimball SR 《American journal of physiology. Cell physiology》2011,300(5):C1172-C1180
The mammalian target of rapamycin (mTOR) is a protein kinase that, when present in a complex referred to as mTOR complex 1 (mTORC1), acts as an important regulator of growth and metabolism. The activity of the complex is regulated through multiple upstream signaling pathways, including those involving Akt and the extracellular-regulated kinase (ERK). Previous studies have shown that, in part, Akt and ERK promote mTORC1 signaling through phosphorylation of a GTPase activator protein (GAP), referred to as tuberous sclerosis complex 2 (TSC2), that acts as an upstream inhibitor of mTORC1. In the present study we extend the earlier studies to show that activation of the Akt and ERK pathways acts in a synergistic manner to promote mTORC1 signaling. Moreover, we provide evidence that the Akt and ERK signaling pathways converge on TSC2, and that Akt phosphorylates residues on TSC2 distinct from those phosphorylated by ERK. The results also suggest that leucine-induced stimulation of mTORC1 signaling occurs through a mechanism distinct from TSC2 and the Akt and ERK signaling pathways. Overall, the results are consistent with a model in which Akt and ERK phosphorylate distinct sites on TSC2, leading to greater repression of its GAP activity, and consequently a magnified stimulation of mTORC1 signaling, when compared with either input alone. The results further suggest that leucine acts through a mechanism distinct from TSC2 to stimulate mTORC1 signaling. 相似文献
143.
Kiyoi T Adam JM Clark JK Davies K Easson AM Edwards D Feilden H Fields R Francis S Jeremiah F McArthur D Morrison AJ Prosser A Ratcliffe PD Schulz J Wishart G Baker J Campbell R Cottney JE Deehan M Epemolu O Evans L 《Bioorganic & medicinal chemistry letters》2011,21(6):1748-1753
Novel 3-(1H-indol-3-yl)-1,2,4-oxadiazoles and -thiadiazoles were synthesized and found to be potent CB1 cannabinoid receptor agonists. The oral bioavailability of these compounds could be dramatically improved by optimization studies of the side chains attached to the indole and oxadiazole cores, leading to identification of a CB1 receptor agonist with good oral activity in a range of preclinical models of antinociception and antihyperalgesia. 相似文献
144.
Many gram-negative enterobacteria produce surface-associated fimbriae that facilitate attachment and adherence to eucaryotic cells and tissues. These organelles are believed to play an important role during infection by enabling bacteria to colonize specific niches within their hosts. One class of these fimbriae is assembled using a periplasmic chaperone and membrane-associated scaffolding protein that has been referred to as an usher because of its function in fimbrial biogenesis. The presence of multiple types of fimbriae assembled by the chaperone/usher pathway can be found both within a single bacterial species and also among different genera. One way of controlling fimbrial assembly in these bacteria is at the genetic level by positively or negatively regulating fimbrial gene expression. This minireview considers the mechanisms that have been described to control fimbrial gene expression and uses specific examples to demonstrate both unique and shared properties of such regulatory mechanisms. 相似文献
145.
Tipton JD Tran JC Catherman AD Ahlf DR Durbin KR Kelleher NL 《The Journal of biological chemistry》2011,286(29):25451-25458
The diverse proteome of an organism arises from such events as single nucleotide substitutions at the DNA level, different RNA processing, and dynamic enzymatic post-translational modifications. This minireview focuses on the measurement of intact proteins to describe the diversity found in proteomes. The field of biological mass spectrometry has steadily advanced, enabling improvements in the characterization of single proteins to proteins derived from cells or tissues. In this minireview, we discuss the basic technology for "top-down" intact protein analysis. Furthermore, examples of studies involved with the qualitative and quantitative analysis of full-length polypeptides are provided. 相似文献
146.
Jan H. Wanink Jeremiah J. Kashindye P.C. Goudswaard Frans Witte 《Freshwater Biology》2001,46(1):75-85
1. We tested the hypothesis that increased hypoxia in Lake Victoria provides a refugium for the cyprinid dagaa ( Rastrineobola argentea ) against hypoxia-sensitive Nile perch ( Lates niloticus ).
2. Hypoxia in the main habitat of dagaa was rare during 1979–80, but lasted 3–5 months in 1987 and 1988, during which time adult dagaa spent the day just above the oxycline instead of near the bottom.
3. Dissolved oxygen concentrations in the layer just above the oxycline were not critical for Nile perch, but a mass kill of this species following a sudden upwelling of hypoxic water suggested that oxycline-dwelling is risky.
4. Our data suggest no difference between dagaa and Nile perch in the level at which dissolved oxygen starts to limit their vertical distribution in the water column, but dagaa seems to be even more sensitive to extreme hypoxia (<1–2 mg O2 L−1) than Nile perch.
5. We argue that oxycline-dwelling dagaa are not seeking a predation refugium but that they are limited by low oxygen levels in reaching their feeding areas near the bottom. 相似文献
2. Hypoxia in the main habitat of dagaa was rare during 1979–80, but lasted 3–5 months in 1987 and 1988, during which time adult dagaa spent the day just above the oxycline instead of near the bottom.
3. Dissolved oxygen concentrations in the layer just above the oxycline were not critical for Nile perch, but a mass kill of this species following a sudden upwelling of hypoxic water suggested that oxycline-dwelling is risky.
4. Our data suggest no difference between dagaa and Nile perch in the level at which dissolved oxygen starts to limit their vertical distribution in the water column, but dagaa seems to be even more sensitive to extreme hypoxia (<1–2 mg O2 L−1) than Nile perch.
5. We argue that oxycline-dwelling dagaa are not seeking a predation refugium but that they are limited by low oxygen levels in reaching their feeding areas near the bottom. 相似文献
147.
Nuclear magnetic resonance structure of the N-terminal domain of nonstructural protein 3 from the severe acute respiratory syndrome coronavirus 总被引:1,自引:1,他引:0 下载免费PDF全文
Serrano P Johnson MA Almeida MS Horst R Herrmann T Joseph JS Neuman BW Subramanian V Saikatendu KS Buchmeier MJ Stevens RC Kuhn P Wüthrich K 《Journal of virology》2007,81(21):12049-12060
This paper describes the structure determination of nsp3a, the N-terminal domain of the severe acute respiratory syndrome coronavirus (SARS-CoV) nonstructural protein 3. nsp3a exhibits a ubiquitin-like globular fold of residues 1 to 112 and a flexibly extended glutamic acid-rich domain of residues 113 to 183. In addition to the four beta-strands and two alpha-helices that are common to ubiquitin-like folds, the globular domain of nsp3a contains two short helices representing a feature that has not previously been observed in these proteins. Nuclear magnetic resonance chemical shift perturbations showed that these unique structural elements are involved in interactions with single-stranded RNA. Structural similarities with proteins involved in various cell-signaling pathways indicate possible roles of nsp3a in viral infection and persistence. 相似文献
148.
149.
The technique of RNA interference (RNAi) was trialed in primary human foreskin fibroblasts, both in monolayer culture and
in the fibroblast-populated collagen matrix. Knockdown of lamin A/C, p53, and FAK was possible with low-confluency (<50%)
monolayer fibroblasts, a transfection vehicle concentration of 1%, and an siRNA concentration of 25–50 nM. Knockdown also
was possible in the collagen matrix using similar reagent concentrations and a cellular density of one million fibroblasts
per ml of matrix. Optimization of transfection conditions appeared to be important to increase knockdown efficiency. Consistent
with prediction, knockdown of FAK induced apoptosis in the fibroblast-populated collagen matrix. 相似文献
150.
Mechanical forces play a key role in crucial cellular processes involving force-bearing biomolecules, as well as in novel single-molecule pulling experiments. We present an exact method that enables one to extrapolate, to low (or zero) forces, entire time-correlation functions and kinetic rate constants from the conformational dynamics either simulated numerically or measured experimentally at a single, relatively higher, external force. The method has twofold relevance: 1), to extrapolate the kinetics at physiological force conditions from molecular dynamics trajectories generated at higher forces that accelerate conformational transitions; and 2), to extrapolate unfolding rates from experimental force-extension single-molecule curves. The theoretical formalism, based on stochastic path integral weights of Langevin trajectories, is presented for the constant-force, constant loading rate, and constant-velocity modes of the pulling experiments. For the first relevance, applications are described for simulating the conformational isomerization of alanine dipeptide; and for the second relevance, the single-molecule pulling of RNA is considered. The ability to assign a weight to each trace in the single-molecule data also suggests a means to quantitatively compare unfolding pathways under different conditions. 相似文献