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991.
Zhou H Lapointe BM Clark SR Zbytnuik L Kubes P 《Journal of immunology (Baltimore, Md. : 1950)》2006,177(11):8103-8110
To study the mechanisms involved in leukocyte recruitment induced by local bacterial infection within the CNS, we used intravital microscopy to visualize the interaction between leukocytes and the microvasculature in the brain. First, we showed that intracerebroventricular injection of LPS could cause significant rolling and adhesion of leukocytes in the brain postcapillary venules of wild-type mice, while negligible recruitment was observed in TLR4-deficient C57BL/10ScCr mice and CD14 knockout mice, suggesting recruitment is mediated by TLR4/CD14-bearing cells. Moreover, we observed reduced but not complete inhibition of recruitment in MyD88 knockout mice, indicating both MyD88-dependent and -independent pathways are involved. The leukocyte recruitment responses in chimeric mice with TLR4-positive microglia and endothelium, but TLR4-negative leukocytes, were comparable to normal wild-type mice, suggesting either endothelium or microglia play a crucial role in the induction of leukocyte recruitment. LPS injection induced both microglial and endothelial activation in the CNS. Furthermore, minocycline, an effective inhibitor of microglial activation, completely blocked the rolling and adhesion of leukocytes in the brain and blocked TNF-alpha production in response to LPS in vivo. Minocycline did not affect activation of endothelium by LPS in vitro. TNFR p55/p75 double knockout mice also exhibited significant reductions in both rolling and adhesion in response to LPS, indicating TNF-alpha signaling is critical for the leukocyte recruitment. Our results identify a TLR4 detection system within the blood-brain barrier. The microglia play the role of sentinel cells detecting LPS thereby inducing endothelial activation and leading to efficient leukocyte recruitment to the CNS. 相似文献
992.
Postle AD Gonzales LW Bernhard W Clark GT Godinez MH Godinez RI Ballard PL 《Journal of lipid research》2006,47(6):1322-1331
Maturation of fetal alveolar type II epithelial cells in utero is characterized by specific changes to lung surfactant phospholipids. Here, we quantified the effects of hormonal differentiation in vitro on the molecular specificity of cellular and secreted phospholipids from human fetal type II epithelial cells using electrospray ionization mass spectrometry. Differentiation, assessed by morphology and changes in gene expression, was accompanied by restricted and specific modifications to cell phospholipids, principally enrichments of shorter chain species of phosphatidylcholine (PC) and phosphatidylinositol, that were not observed in fetal lung fibroblasts. Treatment of differentiated epithelial cells with secretagogues stimulated the secretion of functional surfactant-containing surfactant proteins B and C (SP-B and SP-C). Secreted material was further enriched in this same set of phospholipid species but was characterized by increased contents of short-chain monounsaturated and disaturated species other than dipalmitoyl PC (PC16:0/16:0), principally palmitoylmyristoyl PC (PC16:0/14:0) and palmitoylpalmitoleoyl PC (PC16:0/16:1). Mixtures of these PC molecular species, phosphatidylglycerol, and SP-B and SP-C were functionally active and rapidly generated low surface tension on compression in a pulsating bubble surfactometer. These results suggest that hormonally differentiated human fetal type II cells do not select the molecular composition of surfactant phospholipid on the basis of saturation but, more likely, on the basis of acyl chain length. 相似文献
993.
We have identified a series of potent cholesteryl ester transfer protein (CETP) inhibitors, one member of which, torcetrapib, is undergoing phase 3 clinical trials. In this report, we demonstrate that these inhibitors bind specifically to CETP with 1:1 stoichiometry and block both neutral lipid and phospholipid (PL) transfer activities. CETP preincubated with inhibitor subsequently bound both cholesteryl ester and PL normally; however, binding of triglyceride (TG) appeared partially reduced. Inhibition by torcetrapib could be reversed by titration with both native and synthetic lipid substrates, especially TG-rich substrates, and occurred to an equal extent after long or short preincubations. The reversal of TG transfer inhibition using substrates containing TG as the only neutral lipid was noncompetitive, suggesting that the effect on TG binding was indirect. Analysis of the CETP distribution in plasma demonstrated increased binding to HDL in the presence of inhibitor. Furthermore, the degree to which plasma CETP shifted from a free to an HDL-bound state was tightly correlated to the percentage inhibition of CE transfer activity. The finding by surface plasmon resonance that torcetrapib increases the affinity of CETP for HDL by approximately 5-fold likely represents a shift to a binding state that is nonpermissive for lipid transfer. In summary, these data are consistent with a mechanism whereby this series of inhibitors block all of the major lipid transfer functions of plasma CETP by inducing a nonproductive complex between the transfer protein and HDL. 相似文献
994.
Previous studies have shown that the ability of Mycobacterium tuberculosis to block a Ca(2+) flux is an important step in its capacity to halt phagosome maturation. This affect on Ca(2+) release results from M. tuberculosis inhibition of sphingosine kinase (SPK) activity. However, these studies did not address the potential role of SPK and Ca(2+) in other aspects of macrophage activation including production of proinflammatory mediators. We previously showed that nonpathogenic Mycobacterium smegmatis and to a lesser extent pathogenic Mycobacterium avium, activate Ca(2+)-dependent calmodulin/calmodulin kinase and MAPK pathways in murine macrophages leading to TNF-alpha production. However, whether SPK functions in promoting MAPK activation upon mycobacterial infection was not defined in these studies. In the present work we found that SPK is required for ERK1/2 activation in murine macrophages infected with either M. avium or M. smegmatis. Phosphoinositide-specific phospholipase C (PI-PLC) and conventional protein kinase C (cPKC) were also important for ERK1/2 activation. Moreover, there was increased activation of cPKC and PI3K in macrophages infected with M. smegmatis compared with M. avium. This cPKC and PI3K activation was dependent on SPK and PI-PLC. Finally, in macrophages infected with M. smegmatis compared with M. avium, we observed enhanced secretion of TNF-alpha, IL-6, RANTES, and G-CSF and found production of these inflammatory mediators to be dependent on SPK, PI-PLC, cPKC, and PI3K. These studies are the first to show that the macrophage proinflammatory response following a mycobacterial infection is regulated by SPK/PI-PLC/PKC activation of ERK1/2 and PI3K pathways. 相似文献
995.
Reconciling Carbon-cycle Concepts, Terminology, and Methods 总被引:5,自引:1,他引:4
F. S. Chapin III G. M. Woodwell J. T. Randerson E. B. Rastetter G. M. Lovett D. D. Baldocchi D. A. Clark M. E. Harmon D. S. Schimel R. Valentini C. Wirth J. D. Aber J. J. Cole M. L. Goulden J. W. Harden M. Heimann R. W. Howarth P. A. Matson A. D. McGuire J. M. Melillo H. A. Mooney J. C. Neff R. A. Houghton M. L. Pace M. G. Ryan S. W. Running O. E. Sala W. H. Schlesinger E.-D. Schulze 《Ecosystems》2006,9(7):1041-1050
Recent projections of climatic change have focused a great deal of scientific and public attention on patterns of carbon (C)
cycling as well as its controls, particularly the factors that determine whether an ecosystem is a net source or sink of atmospheric
carbon dioxide (CO2). Net ecosystem production (NEP), a central concept in C-cycling research, has been used by scientists to represent two different
concepts. We propose that NEP be restricted to just one of its two original definitions—the imbalance between gross primary
production (GPP) and ecosystem respiration (ER). We further propose that a new term—net ecosystem carbon balance (NECB)—be
applied to the net rate of C accumulation in (or loss from [negative sign]) ecosystems. Net ecosystem carbon balance differs
from NEP when C fluxes other than C fixation and respiration occur, or when inorganic C enters or leaves in dissolved form.
These fluxes include the leaching loss or lateral transfer of C from the ecosystem; the emission of volatile organic C, methane,
and carbon monoxide; and the release of soot and CO2 from fire. Carbon fluxes in addition to NEP are particularly important determinants of NECB over long time scales. However,
even over short time scales, they are important in ecosystems such as streams, estuaries, wetlands, and cities. Recent technological
advances have led to a diversity of approaches to the measurement of C fluxes at different temporal and spatial scales. These
approaches frequently capture different components of NEP or NECB and can therefore be compared across scales only by carefully
specifying the fluxes included in the measurements. By explicitly identifying the fluxes that comprise NECB and other components
of the C cycle, such as net ecosystem exchange (NEE) and net biome production (NBP), we can provide a less ambiguous framework
for understanding and communicating recent changes in the global C cycle. 相似文献
996.
Determinants of Leaf Litter Nutrient Cycling in a Tropical Rain Forest: Soil Fertility Versus Topography 总被引:1,自引:0,他引:1
We investigated the influence of landscape-level variation in soil fertility and topographic position on leaf litter nutrient
dynamics in a tropical rain forest in Costa Rica. We sampled across the three main edaphic conditions (ultisol slope, ultisol
plateau, and inceptisol) to determine the effect of soil nutrients on leaf litter nutrient concentrations while controlling
for topography, and to examine topographic effects while controlling for soil nutrients. Both leaf litter macronutrient [phosphorus
(P), nitrogen (N), sulfur (S), calcium (Ca), potassium (K), magnesium (Mg)] and micronutrient concentrations were quantified
throughout a 4-year period. Leaf litter [P], [N] and [K] varied significantly among soil types. The variation in [P], [N],
and [K] was explained by soil fertility alone. Leaf litter [S], [Ca], and [Mg] did not vary among the three soil types. Macronutrient
(P, K, Mg, S, Ca) concentrations in the leaf litter were much less variable than those of Fe and Al. Lower variability in
essential plant nutrients suggests a great deal of plant control over the amount of nutrients resorbed before senescense.
Leaf litter macronutrient concentrations varied significantly over the 4-year period, but the temporal variation did not differ
among the three edaphic types as anticipated. Hence, although the magnitude of nutrient fluxes may be controlled by local
factors such as soil fertility, temporal patterns are likely regulated by a common environmental variable such as precipitation
or temperature. 相似文献
997.
Fisheries bioeconomics: why is it so widely misunderstood? 总被引:1,自引:0,他引:1
Colin W. Clark 《Population Ecology》2006,48(2):95-98
Many fisheries management systems, even when based on apparently sound science, have failed to prevent severe overfishing. And even when successful in this sense, such systems have frequently resulted in a large degree of excess fishing capacity. The reason for these failures can often be found in a lack of consideration of the economic incentives affecting fishermen. Specifically, when forced to compete for a fixed total annual catch quota (TAC), fishermen are motivated to fish at high intensity, and to expand the fishing power of their vessels. Individual fishing quotas (IFQs) are being increasingly used as a method of altering economic incentives in a desirable way. IFQ systems, however, can also suffer severe shortcomings, unless substantial fees are extracted for the exclusive right to exploit a publicly owned resource. When combined with appropriate fees, or royalties, IFQs can indeed result in sustainable, profitable fisheries. There still remains the fundamental question of risk management, but this is also now beginning to be addressed. Thus there is now a strong hope for the future success of marine fisheries, at least within 200-mile coastal zones. 相似文献
998.
The specific aim of this study was to investigate the effect of chondroitinase ABC treatment on the frictional response of bovine articular cartilage against glass, under creep loading. The hypothesis is that chondroitinase ABC treatment increases the friction coefficient of bovine articular cartilage under creep. Articular cartilage samples (n = 12) harvested from two bovine knee joints (1-3 months old) were divided into a control group (intact specimens) and a treated group (chondroitinase ABC digestion), and tested in unconfined compression with simultaneous continuous sliding (+/- 4 mm at 1 mm/s) under a constant applied stress of 0.5 MPa, for 2500 s. The time-dependent response of the friction coefficient was measured. With increasing duration of loading, treated samples exhibited a significantly higher friction coefficient than control samples as assessed by the equilibrium value (treated: micro(eq) = 0.19 +/- 0.02; control: micro(eq) = 0.12 +/- 0.03; p = 0.002), though the coefficient achieved immediately upon loading did not increase significantly (treated: micro(min) = 0.0053 +/- 0.0025; control: micro(min) = 0.037 +/- 0.0013; p = 0.19). Our results demonstrate that removal of the cartilage glycosaminoglycans using chondroitinase ABC significantly increases the overall time-dependent friction coefficient of articular cartilage. These findings strengthen the motivation for developing chondroprotective strategies by increasing cartilage chondroitin sulfate content in osteoarthritic joints. 相似文献
999.
In recent years it has been recognized that bacteriophages have several potential applications in the modern biotechnology industry: they have been proposed as delivery vehicles for protein and DNA vaccines; as gene therapy delivery vehicles; as alternatives to antibiotics; for the detection of pathogenic bacteria; and as tools for screening libraries of proteins, peptides or antibodies. This diversity, and the ease of their manipulation and production, means that they have potential uses in research, therapeutics and manufacturing in both the biotechnology and medical fields. It is hoped that the wide range of scientists, clinicians and biotechnologists currently researching or putting phages to practical use are able to pool their knowledge and expertise and thereby accelerate progress towards further development in this exciting field of biotechnology. 相似文献
1000.