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1.
Hair cells of the inner ear develop from an equivalence group marked by expression of the proneural gene Atoh1. In mouse, Atoh1 is necessary for hair cell differentiation, but its role in specifying the equivalence group (proneural function) has been questioned and little is known about its upstream activators. We have addressed these issues in zebrafish. Two zebrafish homologs, atoh1a and atoh1b, are together necessary for hair cell development. These genes crossregulate each other but are differentially required during distinct developmental periods, first in the preotic placode and later in the otic vesicle. Interactions with the Notch pathway confirm that atoh1 genes have early proneural function. Fgf3 and Fgf8 are upstream activators of atoh1 genes during both phases, and foxi1, pax8 and dlx genes regulate atoh1b in the preplacode. A model is presented in which zebrafish atoh1 genes operate in a complex network leading to hair cell development. 相似文献
2.
Geerts WJ Vocking K Schoonen N Haarbosch L van Donselaar EG Regan-Klapisz E Post JA 《Journal of structural biology》2011,(3):350-359
Primary cilia are microtubule based sensory organelles that play an important role in maintaining cellular homeostasis. Malfunctioning results in a number of abnormalities, diseases (ciliopathies) and certain types of cancer. Morphological and biochemical knowledge on cilia/flagella, (early) ciliogenesis and intraflagellar transport is often obtained from model systems (e.g. Chlamydomonas) or from multi ciliary cells like lung or kidney epithelium.In this study endothelial cells in isolated human umbilical veins (HUVs) and cultured human umbilical vein endothelial cells (HUVECs) are compared and used to study primary ciliogenesis. By combining fluorescence microscopy, SEM, 2D and 3D TEM techniques we found that under the tested culturing conditions 60% of cobblestone endothelial cells form a primary cilium. Only a few of these cilia are present (protruding) on the endothelial cell surface, meaning that most primary cilia are in the cytoplasm (non-protruding). This was also observed in situ in the endothelial cells in the umbilical vein. The exact function(s?) of these non-protruding cilia remains unclear.Ultra-structural analysis of cultured HUVECs and the endothelial layer of the human umbilical veins reveal that there are: vesicles inside the ciliary pocket during the early stages of ciliogenesis; tubules/vesicles from the cytoplasm fuse with the ciliary sheath; irregular axoneme patterns, and two round, membranous vesicles inside the basal body.We conclude that cobblestone cultured HUVECs are comparable to the in vivo epithelial lining of the umbilical veins and therefore provide a well defined, relatively simple human model system with a reproducible number of non-protruding primary cilia for studying ciliogenesis. 相似文献
3.
Giovanna Della Porta Jeroen A. M. Kenter Juan R. Bahamonde Adrian Immenhauser Elisa Villa 《Facies》2003,49(1):175-207
Summary The Carboniferous, particularly during the Serpukhovian and Bashkirian time, was a period of scarce shallow-water calcimicrobial-microbialite
reef growth. Organic frameworks developed on high-rising platforms are, however, recorded in the Precaspian Basin subsurface,
Kazakhstan, Russia, Japan and Spain and represent uncommon occurrences within the general trend of low accumulation rates
and scarcity of shallow-water reefs. Sierra del Cuera (Cantabrian Mountains, N Spain) is a well-exposed high-rising carbonate
platform of Late Carboniferous (Bashkirian-Moscovian) age with a microbial boundstone-dominated slope dipping from 20° up
to 45°. Kilometer-scale continuous exposures allow the detailed documentation of slope geometry and lithofacies spatial distribution.
This study aims to develop a depositional model of steep-margined Late Paleozoic platforms built by microbial carbonates and
to contribute to the understanding of the controlling factors on lithofacies characteristics, stacking patterns, accumulation
rates and evolution of the depositional architecture of systems, which differ from light-dependent coralgal platform margins.
From the platform break to depths of nearly 300 m, the slope is dominated by massive cement-rich boundstone, which accumulated
through the biologically induced precipitation of micrite. Boundstone facies (type A) with peloidal carbonate mud, fenestellid
and fistuliporid bryozoans, sponge-like molds and primary cavities filled by radiaxial fibrous cement occurs all over the
slope but dominates the deeper settings. Type B boundstone consists of globose centimeter-scale laminated accretionary structures,
which commonly host botryoidal cement in growth cavities. The laminae nucleate around fenestellid bryozoans, sponges, Renalcis and Girvanella-like filaments. Type B boundstone typically occurs at depths between 20–150 m to locally more than 300 m and forms the bulk
of the Bashkirian prograding slope. The uppermost slope boundstone (type C; between 0 and 20–100 m depth) includes peloidal
micrite, radiaxial fibrous cement, bryozoans, sponge molds, Donezella, Renalcis, Girvanella, Ortonella, calcareous algae and calcitornellid foraminifers.
From depths of 80–200 m to 450 m, 1–30 m thick lenses of crinoidal packstone, spiculitic wackestone, and bryozoan biocementstone
with red-stained micrite matrix are episodically intercalated with boundstone and breccias. These layers increase in number
from the uppermost Bashkirian to the Moscovian in parallel with the change from a rapidly prograding to an aggrading architecture.
The red-stained strata share comparable features with Lower Carboniferous deeper-water mud-mound facies and were deposited
during relative rises of sea level and pauses in boundstone production. Rapid relative sea-level rises might have been associated
with changes in oceanographic conditions not favourable for thecalcimicrobial boundstone growth, such as upwelling of colder,
nutrient-rich waters lifting the thermocline to depths of 80–200 m.
Downslope of 150–300 m, boundstones interfinger with layers of matrix-free breccias, lenses of matrix-rich breccias, platform-
and slope-derived grainstone and crinoidal packstone. Clast-supported breccias bound by radiaxial cement are produced by rock
falls and avalanches coeval to boundstone growth. Matrix-rich breccias are debris flow deposits triggered by the accumulation
of red-stained layers. Debris flows develop following the relative sea-level rises, which favour the deposition of micrite-rich
lithofacies on the slope rather than being related to relative sea-level falls and subaerial exposures. The steep slope angles
are the result of in situ growth and rapid stabilization by marine cement in the uppermost part, passing into a detrital talus, which rests at the
angle of repose of noncohesive material. In the Moscovian, the aggradational architecture and steeper clinoforms are the result
of increased accommodation space due to tectonic subsidence and due to a reduction of slope accumulation rates (from 240±45−605±35
m/My to 130±5 m/My). The increasing number of red-stained layers and the decrease of boundstone productivity are attributed
to environmental changes in the adjacent basin, in particular during relative rises of sea level and to possible cooling due
to icehouse conditions. The geometry of the depositional system appears to be controlled by boundstone growth rates. During
the Bashkirian, the boundstone growth potential is at least 10 times greater than average values for ancient carbonate systems.
The slope progradation rates (nearly 400–1000 m/My) are similar to the highest values deduced for the Holocene Bahamian prograding
platform margin. The fundamental differences with modern systems are that progradation of the microbial-boundstone dominated
steep slope is primarily controlled by boundstone growth rates rather than by highstand shedding from the platform top and
that boundstone growth is largely independent from light and controlled by the physicochemical characteristics of seawater. 相似文献
4.
Esmeralda N Blaney Davidson Elly L Vitters Wim B van den Berg Peter M van der Kraan 《Arthritis research & therapy》2006,8(3):R65-8
Cartilage damage in osteoarthritis (OA) is considered an imbalance between catabolic and anabolic factors, favoring the catabolic
side. We assessed whether adenoviral overexpression of transforming growth factor-β (TGFβ) enhanced cartilage repair and whether
TGFβ-induced fibrosis was blocked by local expression of the intracellular TGFβ inhibitor Smad7. We inflicted cartilage damage
by injection of interleukin-1 (IL-1) into murine knee joints. After 2 days, we injected an adenovirus encoding TGFβ. On day
4, we measured proteoglycan (PG) synthesis and content. To examine whether we could block TGFβ-induced fibrosis and stimulate
cartilage repair simultaneously, we injected Ad-TGFβ and Ad-Smad7. This was performed both after IL-1-induced damage and in
a model of primary OA. In addition to PG in cartilage, synovial fibrosis was measured by determining the synovial width and
the number of procollagen I-expressing cells. Adenoviral overexpression of TGFβ restored the IL-1-induced reduction in PG
content and increased PG synthesis. TGFβ-induced an elevation in PG content in cartilage of the OA model. TGFβ-induced synovial
fibrosis was strongly diminished by simultaneous synovial overexpression of Smad7 in the synovial lining. Of great interest,
overexpression of Smad7 did not reduce the repair-stimulating effect of TGFβ on cartilage. Adenoviral overexpression of TGFβ
stimulated repair of IL-1- and OA-damaged cartilage. TGFβ-induced synovial fibrosis was blocked by locally inhibiting TGFβ
signaling in the synovial lining by simultaneously transfecting it with an adenovirus overexpressing Smad7. 相似文献
5.
Elly P. H. Best 《Physiologia plantarum》1986,68(3):502-510
The photosynthetic and growth characteristics of Ceratophyllum demersum L. were investigated under laboratory conditions which simulated those encountered in the plants' normal environment. The carbon fixation rate of C. demersum measured with 14 C at light and carbon saturation at pH 8.0 was 4.48 mg C (g ash-free dry weight)−1 h−1 . It was lower at pH 6.5 than at pH 8.0. The light use efficiencies in quiescent plants and actively growing plants were 6.3 and 8.7 × 10−9 kg CO2 J−1 , respectively, with corresponding maximum photosynthetic rates of 2.67 and 4.36 mg C (g ash-free dry weight)−1 h−1 . Photorespiration in actively growing plants consumed 24% of the carbon fixed. Incubation with DCMU demonstrated that about one-third was refixed. The optimum temperature for carbon fixation was 25°C. The C3 -photosynthetic pathway was the main operational route as indicated by the early photosynthetic products (largely C3 -acids) and the absence of Krantz anatomy and the chlorophyll a:b ratio (2.7). The maximum relative growth rates ranged from 0.025 to 0.041 g ash-free dry weight (g ash-free dry weight)−1 day−1 in the field (Lake Vechten, 1 to 3 m depth classes). 相似文献
6.
Wim E. J. M. Ghijsen Elly Besselsen Vincent Geukers Willem Kamphuis Fernando H. Lopes da Silva 《Journal of neurochemistry》1992,59(2):482-486
The effect of long-term potentiation (LTP) on endogenous amino acid release from rat hippocampus slices was studied. LTP was induced in vivo by application of a tetanus (200 Hz, 200 ms) to the Schaffer collateral fibers in unanesthetized rats. Endogenous release of glutamate and gamma-aminobutyric acid (GABA) was investigated 60 min after tetanization in CA1 subslices of potentiated and control rats. No significant effects of LTP were observed in basal and K(+)-induced Ca(2+)-independent release components of these amino acids. In contrast, K(+)-induced Ca(2+)-dependent release of both glutamate and GABA increased approximately 100% in slices from potentiated rats. No differences were observed in total content of glutamate and GABA between the subslices from control and LTP animals. These results suggest a persistent increase in the recruitment of the presynaptic vesicular pool of glutamate and GABA during LTP. 相似文献
7.
Franco Lori Davide De Forni Elly Katabira Denis Baev Renato Maserati Sandra A. Calarota Pedro Cahn Marco Testori Aza Rakhmanova Michael R. Stevens 《PloS one》2012,7(10)
Background
A new class of antiretrovirals, AntiViral-HyperActivation Limiting Therapeutics (AV-HALTs), has been proposed as a disease-modifying therapy to both reduce Human Immunodeficiency Virus Type 1 (HIV-1) RNA levels and the excessive immune activation now recognized as the major driver of not only the continual loss of CD4+ T cells and progression to Acquired Immunodeficiency Syndrome (AIDS), but also of the emergence of both AIDS-defining and non-AIDS events that negatively impact upon morbidity and mortality despite successful (ie, fully suppressive) therapy. VS411, the first-in-class AV-HALT, combined low-dose, slow-release didanosine with low-dose hydroxycarbamide to accomplish both objectives with a favorable toxicity profile during short-term administration. Five dose combinations were administered as VS411 to test the AV-HALT Proof-of-Concept in HIV-1-infected subjects.Methods
Multinational, double-blind, 28-day Phase 2a dose-ranging Proof-of-Concept study of antiviral activity, immunological parameters, safety, and genotypic resistance in 58 evaluable antiretroviral-naïve HIV-1-infected adults. Randomization and allocation to study arms were carried out by a central computer system. Results were analyzed by ANOVA, Kruskal-Wallis, ANCOVA, and two-tailed paired t tests.Results
VS411 was well-tolerated, produced significant reductions of HIV-1 RNA levels, increased CD4+ T cell counts, and led to significant, rapid, unprecedented reductions of immune activation markers after 28 days despite incomplete viral suppression and without inhibiting HIV-1-specific immune responses. The didanosine 200 mg/HC 900 mg once-daily formulation demonstrated the greatest antiviral efficacy (HIV-1 RNA: −1.47 log10 copies/mL; CD4+ T cell count: +135 cells/mm3) and fewest adverse events.Conclusions
VS411 successfully established the Proof-of-Concept that AV-HALTs can combine antiviral efficacy with rapid, potentially beneficial reductions in the excessive immune system activation associated with HIV-1 disease. Rapid reductions in markers of immune system hyperactivation and cellular proliferation were obtained despite the fact that VS411 did not attain maximal suppression of HIV RNA, suggesting this effect was due to the HALT component.Trial Registration
ITEudraCT 2007-002460-98 相似文献8.
Byakika-Kibwika P Lamorde M Mayito J Nabukeera L Mayanja-Kizza H Katabira E Hanpithakpong W Obua C Pakker N Lindegardh N Tarning J de Vries PJ Merry C 《Malaria journal》2012,11(1):132
ABSTRACT: BACKGROUND: Severe malaria is a medical emergency with high mortality. Prompt achievement of therapeutic concentrations of highly effective anti-malarial drugs reduces the risk of death. The aim of this study was to assess the pharmacokinetics and pharmacodynamics of intravenous artesunate in Ugandan adults with severe malaria. METHODS: Fourteen adults with severe falciparum malaria requiring parenteral therapy were treated with 2.4 mg/kg intravenous artesunate. Blood samples were collected after the initial dose and plasma concentrations of artesunate and dihydroartemisinin measured by solid-phase extraction and liquid chromatography-tandem mass spectrometry. The study was approved by the Makerere University Faculty of Medicine Research and Ethics Committee (Ref2010-015) and Uganda National Council of Science and Technology (HS605) and registered with ClinicalTrials.gov (NCT01122134). RESULTS: All study participants achieved prompt resolution of symptoms and complete parasite clearance with median (range) parasite clearance time of 17 (8-24) hours. Median (range) maximal artesunate concentration (Cmax) was 3260 (1020-164000) ng/mL, terminal elimination half-life (T1/2) was 0.25 (0.1-1.8) hours and total artesunate exposure (AUC) was 727 (290-111256) ngh/mL. Median (range) dihydroartemisinin Cmax was 3140 (1670-9530) ng/mL, with Tmax of 0.14 (0.6 - 6.07) hours and T1/2 of 1.31 (0.8-2.8) hours. Dihydroartemisinin AUC was 3492 (2183-6338) ngh/mL. None of the participants reported adverse events. CONCLUSIONS: Plasma concentrations of artesunate and dihydroartemisinin were achieved rapidly with rapid and complete symptom resolution and parasite clearance with no adverse events. 相似文献
9.
The reversal of cellular differentiation to form proliferating progenitor cells is a critical aspect of regenerative ability in the urodele amphibians. This process has been studied using skeletal muscle during limb or tail regeneration, or dorsal iris epithelium during lens regeneration. An unknown activity in serum triggers cell cycle re-entry from the differentiated state. Here we describe the biochemical properties and fractionation of this serum factor. The factor is a glycoprotein that associates with large molecular weight complexes. The purification and molecular identification of the serum factor represents an important avenue in understanding regenerative ability and dedifferentiation capacity on a molecular basis. 相似文献
10.
Guofeng Wu Jan de Leeuw Andrew K. Skidmore Herbert H. T. Prins Elly P. H. Best Yaolin Liu 《Hydrobiologia》2009,623(1):213-222
Almost 95% of the entire population of the Siberian crane (Grus leucogeranus) winter in Poyang Lake, China, where they forage on the tubers of the submerged aquatic macrophyte Vallisneria spiralis. The Three Gorges Dam on the Yangtze River may possibly affect this food source of the Siberian crane by affecting the light
intensity reaching the top of the V. spiralis canopy. In this study, the photosynthetically active radiation at the top of the V. spiralis canopy (PARtc) in Lake Dahuchi was modeled from 1998 to 2006, and the potential impacts of changes in water level and turbidity on the
underwater light climate of V. spiralis were analyzed. PARtc was calculated from incident irradiance while the losses due to reflection at the water surface, absorption, and scattering
within the water column were taken into consideration. The results indicated significant differences in PARtc between years. Six years of water level and Secchi disk depth records revealed a seasonal switching of the lake from a turbid
state at low water levels in autumn, winter, and spring to a clear state at high water levels during the monsoon in summer.
The highest PARtc occurred at intermediate water levels, which were reached when the Yangtze River forces Lake Dahuchi out of its turbid state
in early summer and the water becomes clear. The intended operation of the Three Gorges Dam, which will increase water levels
in May and June, may advance the moment when Lake Dahuchi switches from turbid to clear. We suggest that this might increase
production of V. spiralis and possibly improve the food habitat conditions for wintering Siberian crane in Poyang Lake.
相似文献
Guofeng WuEmail: |