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101.
102.
CYP3A4 is recognized as the main enzyme involved in the metabolism of drugs and xenobiotics in the human body and its inhibition may lead to undesirable consequences. Stilbenes, including resveratrol, belong to a group of dietary health-promoting compounds that also act as inhibitors of CYP3A4. The aim of this study was to examine the use of computer modeling of enzyme-ligand interactions to analyze and predict the inhibition of structurally related compounds. To this end, an aldehyde group was attached to resveratrol and the interactions of CYP3A4 with resveratrol, its aldehyde analogue (RA) and a known synthetic inhibitor were studied and compared in two biological models. Specifically, the metabolism of testosterone was examined in a human intestine cell line (Caco-2/TC7) and in rat liver microsomes (RLM). The results demonstrated a weak inhibitory effect of RA on CYP3A4, as compared to resveratrol itself, in both biological models. Human CYP3A4 was more susceptible to inhibition than the commonly used model isozyme from rat. Modeling of the binding site of CYP3A4 revealed a combination of three types of interactions: hydrophobic interactions, electrostatic interactions and hydrogen bonds. A docking simulation revealed that the RA lacked an important binding feature, as compared to resveratrol, and that that difference may be responsible for its lower level of affinity for CYP3A4. Software analysis of binding affinity may serve as a predictive tool for designing new therapeutic compounds in terms of inhibition of CYP3A4 and help to reveal the biochemical nature of the interactions of dietary compounds, herbal compounds and drugs whose metabolism is mediated by this enzyme. 相似文献
103.
René Uebe Noa Keren‐Khadmy Natalie Zeytuni Emanuel Katzmann Yotam Navon Geula Davidov Ronit Bitton Jürgen M. Plitzko Dirk Schüler Raz Zarivach 《Molecular microbiology》2018,107(4):542-557
Magnetospirillum gryphiswaldense MSR‐1 synthesizes membrane‐enclosed magnetite (Fe3O4) nanoparticles, magnetosomes, for magnetotaxis. Formation of these organelles involves a complex process comprising key steps which are governed by specific magnetosome‐associated proteins. MamB, a cation diffusion facilitator (CDF) family member has been implicated in magnetosome‐directed iron transport. However, deletion mutagenesis studies revealed that MamB is essential for the formation of magnetosome membrane vesicles, but its precise role remains elusive. In this study, we employed a multi‐disciplinary approach to define the role of MamB during magnetosome formation. Using site‐directed mutagenesis complemented by structural analyses, fluorescence microscopy and cryo‐electron tomography, we show that MamB is most likely an active magnetosome‐directed transporter serving two distinct, yet essential functions. First, MamB initiates magnetosome vesicle formation in a transport‐independent process, probably by serving as a landmark protein. Second, MamB transport activity is required for magnetite nucleation. Furthermore, by determining the crystal structure of the MamB cytosolic C‐terminal domain, we also provide mechanistic insight into transport regulation. Additionally, we present evidence that magnetosome vesicle growth and chain formation are independent of magnetite nucleation and magnetic interactions respectively. Together, our data provide novel insight into the role of the key bifunctional magnetosome protein MamB, and the early steps of magnetosome formation. 相似文献
104.
N. Kondo Manabu Nakadome Keren Zhang Tomoyuki Shiojiri Manabu Shibasaki Kozo Hirata Atsushi Iwata 《International journal of biometeorology》1997,40(2):99-102
The purpose of this study was to investigate whether there are any effects of skin temperature changes on sweating response
in the first few minutes of mild exercise. Six healthy males performed a bicycle exercise at 100 W (50 rpm) for 30 min under
an ambient temperature of 23° C (40% RH). Esophageal temperature (T
es), mean skin temperature (T–
sk), local skin temperature at the lower left scapula (T
sl), local sweating rate (M.
sw), and cutaneous blood flow by laser-Doppler flowmetry (LDF) were measured continuously. Although T
sl decreased markedly just after the onset of sweating, T–
sk did not change. M.
sw did not increase constantly in the early stages of exercise, and there was a temporary interruption in the increase of M.
sw. This interruption in sweating was affected by the rate of change in T
sl rather than by the absolute value of T
sl, since there was a positive and significant correlation between the time of the interruption in the increase of M.
sw and the rate of decrease in T
sl (y=6.47x+0.04; r=0.86, P<0.05). The results suggest that sweating response in the early stages of exercise may be influenced by changes in local skin
temperature due to evaporative cooling.
Received: 31 August 1995 / Revised: 26 February 1996 / Accepted: 26 July 1996, 相似文献
105.
M.-T. Rofe Y. Shacham A. Steinvi L. Barak M. Hareuveni S. Banai G. Keren A. Finkelstein H. Shmilovich 《Netherlands heart journal》2016,24(5):350-354
Objectives
To assess the prevalence of blood type A among patients referred for transcatheter aortic valve implantation (TAVI) and whether it is related to vascular complications.Backgrounds
Vascular complications following TAVI are associated with adverse outcomes. Various blood types, particularly type A, have been shown to be more prevalent in cardiovascular diseases and to be related to prognosis.Methods
The prevalence of various blood types in a cohort of 491 consecutive patients who underwent TAVI was compared with a control group of 6500 consecutive hospitalised patients. The prevalence and predictors of vascular complications and bleeding events were evaluated in the blood type A group and were compared with non-type A patients.Results
The mean age of TAVI patients was 83?±?6 years, and 40?% were males. Patients were divided into two groups: blood type A (n?=?220) and non-type A (n?=?271). Type A was significantly more prevalent in the TAVI group than in the control group (45 vs. 38?%, p?=?0.023). Compared with the non-type A group, patients with blood type A had more major and fatal bleeding (14.5 vs. 8.1?%, p?=?0.027) and more vascular complications (any vascular complication: 24.5 vs. 15.9?% p?=?0.016; major vascular complications: 12.3 vs. 7?% p?=?0.047). In a multivariable analysis, blood type A emerged as a significant and independent predictor for vascular complications and bleeding events.Conclusions
Blood type A is significantly more prevalent in TAVI patients than in the general population and is related to higher rates of vascular and bleeding complications.106.
Effects of salinity and varying boron concentrations on boron uptake and growth of wheat 总被引:1,自引:0,他引:1
Summary Two sandculture experiments were conducted with wheat (Triticum aestivum) to determine the effects of (1) osmotic potential (Ψπ) and (2) fluctuating boron (B) concentrations on B availability (toxicity), shoot growth and leaf concentrations of B of
wheat. The first experiment consisted of growing wheat to the spike emergence stage in sandcultures irrigated with a complete
nutrient solution containing 1.0, 7.5, and 15.0 mg Bl−1 and having Ψπ values of −0.02, −0.07, −0.12, and −0.17 MPa produced by CaCl2−NaCl additions. Statistically, shoot weight was independently influenced by the B and Ψπ treatments but not by their interaction. Only the B treatment had a significant effect on leaf boron concentrations; the
B x Ψπ interaction was nonsignificant with respect to leaf B concentrations.
The second experiment was designed to determine if growth and B uptake of wheat responds to the time integrated mean (TIM)
concentration of B. This experiment consisted of four fixed-B concentrations and four fluctuating-B concentrations designed
to produce two TIM concentrations (3.9 and 7.4 mg Bl−1) approached low to high and vice versa. With respect to shoot weight, there was no statistical difference among treatments
having the same TIM concentration during the 10 week experiment. However, shoot B concentrations differed greatly; they were
higher when the B concentration was progressively increased over the 10 week period. Leaf B concentrations (Y leaf at flowering),
while not as high as the shoot B concentrations, were also higher under the treatment of increasing B concentration, indicating
B uptake rates are higher for mature plants than for seedlings. 相似文献
107.
108.
109.
110.
Towards clarification of the biological role of microcystins, a family of cyanobacterial toxins 总被引:1,自引:0,他引:1
Schatz D Keren Y Vardi A Sukenik A Carmeli S Börner T Dittmann E Kaplan A 《Environmental microbiology》2007,9(4):965-970
Microcystins constitute a serious threat to the quality of drinking water worldwide. These protein phosphatase inhibitors are formed by various cyanobacterial species, including Microcystis sp. Microcystins are produced by a complex microcystin synthetase, composed of peptide synthetases and polyketide synthases, encoded by the mcyA-J gene cluster. Recent phylogenetic analysis suggested that the microcystin synthetase predated the metazoan lineage, thus dismissing the possibility that microcystins emerged as a means of defence against grazing, and their original biological role is not clear. We show that lysis of Microcystis cells, either mechanically or because of various stress conditions, induced massive accumulation of McyB and enhanced the production of microcystins in the remaining Microcystis cells. A rise in McyB content was also observed following exposure to microcystin or the protease inhibitors micropeptin and microginin, also produced by Microcystis. The extent of the stimulation by cell extract was strongly affected by the age of the treated Microcystis culture. Older cultures, or those recently diluted from stock cultures, hardly responded to the components in the cell extract. We propose that lysis of a fraction of the Microcystis population is sensed by the rest of the cells because of the release of non-ribosomal peptides. The remaining cells respond by raising their ability to produce microcystins thereby enhancing their fitness in their ecological niche, because of their toxicity. 相似文献