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91.
92.
H Peltola K Jónsdóttir A Lystad C J Sievers I Kallings 《BMJ (Clinical research ed.)》1982,284(6329):1618-1621
Scandinavia (Denmark, Finland, Iceland, Norway, and Sweden) comprises with mutual borders and 22.3 million inhabitants an area where the socioeconomic and cultural conditions are similar. Epidemic diseases, such as meningococcal infection, might therefore be expected to be uniformly distributed. An epidemiological study in the 10-year period 1970-9 shows, however, remarkable differences in the incidence, age, and serogroup and type distribution, as well as in the general dynamics of the disease. Three epidemics, two caused by different serotypes of group B (Norway and Iceland) and one by group A (Finland) occurred within the observation period. The annual overall incidence was generally around 3/100 000 but increased from fivefold (Finland) to eightfold (northern Norway) during epidemics. The epidemic strains caused infection in over 3000 patients and the loss of at least 250 lives. The overall case fatality rate was 8.6% (range 4.1-13.7%). Men were more susceptible and had a worse prognosis than women of the same age group. The group A epidemic in Finland was influenced by a large vaccination campaign, but this possibility was not feasible in the two other epidemics. 相似文献
93.
Heli T. Viljakainen Yoav Ben-Shlomo Sanjay Kinra Shah Ebrahim Hannah Kuper K. V. Radhakrishna Bharati Kulkarni Jon H. Tobias 《PloS one》2015,10(10)
Background
Fracture risk is rising in countries undergoing rapid rural to urban migration, but whether this reflects an adverse effect of urbanization on intrinsic bone strength, as reflected by bone mineral density (BMD), is currently unknown.Methods
Lumbar spine (LS) and total hip (TH) BMD, and total body fat and lean mass, were obtained from DXA scans performed in the Hyderabad arm of the Indian Migration Study (54% male, mean age 49 years). Sib-pair comparisons were performed between rural-urban migrants (RUM) and rural non-migrated (RNM) siblings (N = 185 sib-pairs).Results
In analyses adjusted for height, gender, age and occupation, rural to urban migration was associated with higher lumbar and hip BMD and greater predicted hip strength; ΔLS BMD 0.030 (0.005, 0.055) g/cm2, ΔTH BMD 0.044 (0.024; 0.064) g/cm2, Δcross-sectional moment of inertia 0.162 (0.036, 0.289) cm4. These differences were largely attenuated after adjusting for body composition, insulin levels and current lifestyle factors ie. years of smoking, alcohol consumption and moderate to vigorous physical activity. Further analyses suggested that differences in lean mass, and to a lesser extent fat mass, largely explained the BMD differences which we observed.Conclusions
Rural to urban migration as an adult is associated with higher BMD and greater predicted hip strength, reflecting associated alterations in body composition. It remains to be seen how differences in BMD between migration groups will translate into fracture risk in becoming years. 相似文献94.
Iina Vainio Amna Abu Khamidakh Michelangelo Paci Heli Skottman Kati Juuti-Uusitalo Jari Hyttinen Soile Nymark 《PloS one》2015,10(6)
Objective
Computational models of calcium (Ca2+) signaling have been constructed for several cell types. There are, however, no such models for retinal pigment epithelium (RPE). Our aim was to construct a Ca2+ signaling model for RPE based on our experimental data of mechanically induced Ca2+ wave in the in vitro model of RPE, the ARPE-19 monolayer.Methods
We combined six essential Ca2+ signaling components into a model: stretch-sensitive Ca2+ channels (SSCCs), P2Y2 receptors, IP3 receptors, ryanodine receptors, Ca2+ pumps, and gap junctions. The cells in our epithelial model are connected to each other to enable transport of signaling molecules. Parameterization was done by tuning the above model components so that the simulated Ca2+ waves reproduced our control experimental data and data where gap junctions were blocked.Results
Our model was able to explain Ca2+ signaling in ARPE-19 cells, and the basic mechanism was found to be as follows: 1) Cells near the stimulus site are likely to conduct Ca2+ through plasma membrane SSCCs and gap junctions conduct the Ca2+ and IP3 between cells further away. 2) Most likely the stimulated cell secretes ligand to the extracellular space where the ligand diffusion mediates the Ca2+ signal so that the ligand concentration decreases with distance. 3) The phosphorylation of the IP3 receptor defines the cell’s sensitivity to the extracellular ligand attenuating the Ca2+ signal in the distance.Conclusions
The developed model was able to simulate an array of experimental data including drug effects. Furthermore, our simulations predict that suramin may interfere ligand binding on P2Y2 receptors or accelerate P2Y2 receptor phosphorylation, which may partially be the reason for Ca2+ wave attenuation by suramin. Being the first RPE Ca2+ signaling model created based on experimental data on ARPE-19 cell line, the model offers a platform for further modeling of native RPE functions. 相似文献95.
Kv2.1 is a potassium channel α-subunit abundantly expressed throughout the brain. It is a main component of delayed rectifier current (I(K)) in several neuronal types and a regulator of excitability during high-frequency firing. Here we identify AMIGO (amphoterin-induced gene and ORF), a neuronal adhesion protein with leucine-rich repeat and immunoglobin domains, as an integral part of the Kv2.1 channel complex. AMIGO shows extensive spatial and temporal colocalization and association with Kv2.1 in the mouse brain. The colocalization of AMIGO and Kv2.1 is retained even during stimulus-induced changes in Kv2.1 localization. AMIGO increases Kv2.1 conductance in a voltage-dependent manner in HEK cells. Accordingly, inhibition of endogenous AMIGO suppresses neuronal I(K) at negative membrane voltages. In conclusion, our data indicate AMIGO as a function-modulating auxiliary subunit for Kv2.1 and thus provide new insights into regulation of neuronal excitability. 相似文献
96.
Background
Workplace contamination by the use of volatile anesthetic agents should be kept to a minimum if a potential health hazard is to be minimised. Mask induction of animals is a common procedure. The present study investigates the efficiency of a novel scavenging double mask in reducing waste gas concentrations in the breathing zone of the anesthetist performing this procedure. 相似文献97.
98.
Amankwah EK Wang Q Schildkraut JM Tsai YY Ramus SJ Fridley BL Beesley J Johnatty SE Webb PM Chenevix-Trench G;Australian Ovarian Cancer Study Group Dale LC Lambrechts D Amant F Despierre E Vergote I Gayther SA Gentry-Maharaj A Menon U Chang-Claude J Wang-Gohrke S Anton-Culver H Ziogas A Dörk T Dürst M Antonenkova N Bogdanova N Brown R Flanagan JM Kaye SB Paul J Bützow R Nevanlinna H Campbell I Eccles DM Karlan BY Gross J Walsh C Pharoah PD Song H Krüger Kjær S Høgdall E Høgdall C Lundvall L 《PloS one》2011,6(5):e19642
Alterations in stromal tissue components can inhibit or promote epithelial
tumorigenesis. Decorin (DCN) and lumican (LUM)
show reduced stromal expression in serous epithelial ovarian cancer (sEOC). We
hypothesized that common variants in these genes associate with risk.
Associations with sEOC among Caucasians were estimated with odds ratios (OR)
among 397 cases and 920 controls in two U.S.-based studies (discovery set), 436
cases and 1,098 controls in Australia (replication set 1) and a consortium of 15
studies comprising 1,668 cases and 4,249 controls (replication set 2). The
discovery set and replication set 1 (833 cases and 2,013 controls) showed
statistically homogeneous (Pheterogeneity≥0.48) decreased risks of
sEOC at four variants: DCN rs3138165, rs13312816 and rs516115,
and LUM rs17018765 (OR = 0.6 to 0.9;
Ptrend = 0.001 to 0.03). Results from
replication set 2 were statistically homogeneous
(Pheterogeneity≥0.13) and associated with increased risks at
DCN rs3138165 and rs13312816, and LUM
rs17018765: all ORs = 1.2; Ptrend≤0.02. The
ORs at the four variants were statistically heterogeneous across all 18 studies
(Pheterogeneity≤0.03), which precluded combining. In post-hoc
analyses, interactions were observed between each variant and recruitment period
(Pinteraction≤0.003), age at diagnosis
(Pinteraction = 0.04), and year of diagnosis
(Pinteraction = 0.05) in the five studies
with available information (1,044 cases, 2,469 controls). We conclude that
variants in DCN and LUM are not directly
associated with sEOC, and that confirmation of possible effect modification of
the variants by non-genetic factors is required. 相似文献
99.
Elovaara H Kidron H Parkash V Nymalm Y Bligt E Ollikka P Smith DJ Pihlavisto M Salmi M Jalkanen S Salminen TA 《Biochemistry》2011,50(24):5507-5520
Human membrane primary amine oxidase (hAOC3; also known as vascular adhesion protein-1, VAP-1) is expressed upon inflammation in most tissues, where its enzymatic activity plays a crucial role in leukocyte trafficking. We have determined two new structures of a soluble, proteolytically cleaved form of hAOC3 (sAOC3), which was extracted from human plasma. In the 2.6 ? sAOC3 structure, an imidazole molecule is hydrogen bonded to the topaquinone (TPQ) cofactor, which is in an inactive on-copper conformation, while in the 2.95 ? structure, an imidazole molecule is covalently bound to the active off-copper conformation of TPQ. A second imidazole bound by Tyr394 and Thr212 was identified in the substrate channel. We furthermore demonstrated that imidazole has an inhibitory role at high concentrations used in crystallization. A triple mutant (Met211Val/Tyr394Asn/Leu469Gly) of hAOC3 was previously reported to change substrate preferences toward those of hAOC2, another human copper-containing monoamine oxidase. We now mutated these three residues and Thr212 individually to study their distinct role in the substrate specificity of hAOC3. Using enzyme activity assays, the effect of the four single mutations was tested with four different substrates (methylamine, benzylamine, 2-phenylethylamine, and p-tyramine), and their binding modes were predicted by docking studies. As a result, Met211 and Leu469 were shown to be key residues for substrate specificity. The native structures of sAOC3 and the mutational data presented in this study will aid the design of hAOC3 specific inhibitors. 相似文献
100.