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31.
Krushkal J; Xiong M; Ferrell R; Sing CF; Turner ST; Boerwinkle E 《Human molecular genetics》1998,7(9):1379-1383
Elevated blood pressure is an important risk factor for renal-, cerebro-
and cardiovascular diseases. We used an efficient discordant sib-pair
ascertainment scheme to investigate the impact of the distal end of the
long arm of human chromosome 5 (chromosomal region 5q31.1-qter) containing
genes for the alpha1B and beta2 adrenergic receptors and the dopamine
receptor type 1A on variation of systolic blood pressure in young
Caucasians. We measured eight highly polymorphic markers spanning this
positional candidate gene-rich region in 427 individuals from 55
three-generation pedigrees containing 69 discordant sibling pairs, and
calculated multipoint identity by descent (MIBD) probabilities. The results
of genetic linkage and association tests indicate that the region between
markers D5S2093 and D5S462 is significantly linked to one or more
polymorphic genes influencing interindividual variation in systolic blood
pressure levels. Since the alpha1B adrenergic receptor and dopamine
receptor type 1A genes are located close to these markers, these data
suggest that genetic variation in one or both of these G protein-coupled
receptors, which participate in the control of vascular tone, plays an
important role in influencing interindividual variation in systolic blood
pressure levels.
相似文献
32.
Chen BF Chen PJ Jow GM Sablon E Liu CJ Chen DS Kao JH 《Journal of medical virology》2004,74(4):536-542
The clinical relevance of hepatitis B virus (HBV) genotypes has been documented; however, the prevalence of mixed HBV genotype infections in at-risk groups remains controversial. The HBV genotypes were determined in 325 HBV-infected intravenous drug users (IVDU) who were at a greater risk of multiple exposures to different HBV genotypes by using a newly developed line probe assay. The distribution of HBV genotype was as follows: genotype A alone in 2 (0.6%); genotype B alone in 256 (78.8%); genotype C alone in 10 (3.1%); mixed genotype A and B in 18 (5.5%); genotype B and C in 30 (9.2%); genotype B and D in 1 (0.3%); genotype A and C in 1 (0.3%); and mixed infections of genotype A, B, and C in 3 (0.9%). Clonal analysis confirmed further the existence of mixed genotype infection and recombination between different genotypes. Compared with our previous data, the line probe assay seemed more sensitive than polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) assay in identifying HBV genotype (98.8% vs. 65.0%) and detecting mixed genotype infections (16.3% vs. 0%). In conclusion, the prevalence of mixed HBV infections is substantially higher in IVDU in endemic areas, and the line probe assay is a useful method for rapid genotyping of HBV, with particular reference to the detection of mixed genotype infections. 相似文献
33.
C I Pratt S Q Wu M Bhattacharya C Kao K W Gilchrist C A Reznikoff 《Cancer Genetics and Cytogenetics》1992,59(2):180-190
Tumorigenic transformation of SV40-immortalized human uroepithelial cells (SV-HUC) after transfection with EJ/ras was previously reported to be a rare event. To test the hypothesis that ras transformation requires loss of suppressor genes, somatic cell hybrids were generated between a rare tumorigenic transformant and an isogeneic nontumorigenic EJ/ras transfectant obtained in the same experiment. Both parental cell lines, as well as all hybrid progeny, expressed mutant p21 ras protein, but injections of three such independent hybrids into athymic nude mice at passage (P) 4 demonstrated that tumorigenicity was suppressed at 20 of 22 sites. Two tumors developed, after a relatively long 17-week latent period, as compared with a 4-week latent period for the tumorigenic parent. All three hybrids produced tumors at P8, but these showed different latent periods (3-14 weeks). Revertant hybrid tumors were high-grade carcinomas. Cell lines derived from these tumors expressed mutant p21 ras and retained at least 1 EJ/ras integration site. Karyotypic analysis of six independent hybrid tumor revertants showed that each had a unique clonal karyotype. Losses of two or more homologues of 1p, 3p, 4, 8, 10p, 11p, 13q, and 18 were identified in one or more tumorigenic revertants. Losses of all these chromosomes were previously associated with transformation of SV-HUC by EJ/ras, but were also associated with chemical transformation of SV-HUC in tumors that did not express mutant ras. Genetic losses involving most of these chromosomes have also been identified in clinical bladder cancers (i.e., 1p, 3p, 8, 11p, 13 and 18q). These data show that expression of EJ/ras does not negate or significantly alter requirements for multiple genetic losses in HUC tumorigenesis. 相似文献
34.
Lin CT Kao HJ Lin JL Chan WY Wu HC Liang ST 《Laboratory investigation; a journal of technical methods and pathology》2000,80(8):1149-1160
Many nasopharyngeal carcinoma (NPC) biopsy specimens contain Epstein-Barr virus (EBV). However, the response of NPC cells to EBV infection in vitro and in vivo is not well characterized. In this experiment we infected NPC cells with EBV particles through endocytosis of a complex of EBV immunoglobulin A (IgA) secretory component (SC) protein to observe the response of host cells to the foreign viral infection in vitro. We found that EBV particles were endocytosed and stabilized in NPC nuclei 24 hours after infection; the EBV genomes were then gradually decreased after serial passages within 3 to 4 weeks by the following pathway: the EBV genomes first moved toward the nuclear envelope from the center of the nucleus; after crossing the nuclear envelope, they moved into the cytoplasm and toward the plasma membrane and were discharged by exocytosis. At the 10th day of EBV infection, EBV-latent membrane protein-1 and Epstein-Barr nuclear antigen (EBNA)-1 protein expressions could be detected, but not EBV-viral capsid antigen. Observation of EBNA-1 protein and host growth factor and cytokine gene expressions in the weeks after incubation revealed that the EBNA-1 protein expression was decreased proportionally with decrease of EBV genome. The mRNA expression of epithelial growth factor receptor, transforming growth factor (TGF)-alpha, interleukin (IL)-1beta, IL-6, and granulocyte-macrophage colony-stimulating factor increased within 1 to 2 weeks after infection, and gradually recovered to the original level at 3 to 4 weeks, whereas the mRNAs of TGFbeta1, TGFbeta receptor type I (TGFbetaRI), TGFbetaR type II, IL-8, and tumor necrosis factor-alpha remained unchanged. It is concluded that in vitro EBV infection in NPC cells results in increase of certain growth factor and cytokine gene expressions in host cells. The change in gene expression returns to the original level approximately 3 to 4 weeks after infection because of exocytosis of EBV DNA by the infected cells through an unidentified mechanism. 相似文献
35.
The capacity of T cells to bind peptide/MHC ligands changes with T cell development and differentiation. Here we study changes in peptide/MHC multimer binding following T cell activation. Surprisingly, T cell activation caused a marked reduction in specific peptide/MHC Class I multimer binding, which was distinct from transient TCR down-regulation, and was especially dramatic for engagement with low-affinity peptide/MHC ligands. Direct CD8-Class I interactions were also profoundly and rapidly impaired following T cell stimulation, even though surface CD8alpha and CD8beta levels were unchanged after activation, suggesting that decreased CD8 co-receptor binding contributes to this effect. Finally, we show that enzymatic desialylation restores much of the multimer binding on activated T cells, suggesting that altered glycosylation may inhibit TCR/CD8 binding to peptide/MHC ligands. These radical changes in activated T cells' ability to perceive peptide/MHC ligands may contribute to selective outgrowth of clones with high affinity for the stimulatory ligand. 相似文献
36.
Influence of vascular parameters on the effectiveness of intra-aortic balloon pumping: A model study
The intra-aortic balloon pump has been widely used as a temporary heart-assist device. In this investigation, a nonlinear
mathematical model of the arterial system and intra-aortic balloon pump was studied analytically. Thus, the influences of
a number of vascular parameters on the effectiveness of intra-aortic balloon pumping (IABP) were determined. The effects of
changes in vascular parameters of the model on a number of performance indexes were investigated. These performance indexes
(aortic mean diastolic pressure, aortic end diastolic pressure, cardiac output, coronary flow and phase differences between
the fundamental Fourier components of aortic root pressure and flow) were used as the criterion for an evaluation of the effectiveness
of the assist pump. The following vascular parameters were perturbed by four steps (±10%, ±20%) from the values in the standard
model: heart rate, peripheral resistance, left ventricular pressure, aortic elastance, aortic radius, arterial wall thickness,
and aortic length. This model was evaluated for a wide range of balloon-pump phase-control settings (assisted case) and for
the unassisted case (when the pump is disabled). It is concluded that changes in heart rate, peripheral resistance and left
ventricular pressure cause the most significant changes in pump performance.
Dr. Ohley is with the Datascope Corporation
Dr. Kao is with the Technicare Corporation 相似文献
37.
38.
A protein kinase A-dependent molecular switch in synapsins regulates neurite outgrowth 总被引:5,自引:0,他引:5
Kao HT Song HJ Porton B Ming GL Hoh J Abraham M Czernik AJ Pieribone VA Poo MM Greengard P 《Nature neuroscience》2002,5(5):431-437
Cyclic AMP (cAMP) promotes neurite outgrowth in a variety of neuronal cell lines through the activation of protein kinase A (PKA). We show here, using both Xenopus laevis embryonic neuronal culture and intact X. laevis embryos, that the nerve growth-promoting action of cAMP/PKA is mediated in part by the phosphorylation of synapsins at a single amino acid residue. Expression of a mutated form of synapsin that prevents phosphorylation at this site, or introduction of phospho-specific antibodies directed against this site, decreased basal and dibutyryl cAMP-stimulated neurite outgrowth. Expression of a mutation mimicking constitutive phosphorylation at this site increased neurite outgrowth, both under basal conditions and in the presence of a PKA inhibitor. These results provide a potential molecular approach for stimulating neuron regeneration, after injury and in neurodegenerative diseases. 相似文献
39.
Fa-Ten Kao Suhong Tong Yiping Shen Jingwei Yu 《Somatic Cell and Molecular Genetics》1996,22(3):191-199
Three region-specific libraries for the entire human chromosome 18 were constructed using microdissection and MboI linker-adaptor
microcloning techniques. The libraries included 18pter-p11.1 (designated 18P library), 18q 11.1-q12.3 (18Q1 library), and
18q21.1-qter (18Q2 library). Samples of the microclones from each library were analyzed in detail. The insert sizes ranged
between 50–600 bp, with a mean of 180–220 bp for the three libraries. The libraries contained approximately 40–60% microclones
with unique sequence inserts. More than 30 unique sequence microclones from each library were analyzed by Southern blot hybridization
to demonstrate that they are human specific and were derived from chromosome 18. The human gemomic HindIII fragments hybridized
to each microclone were determined and microclones crosshybridized to rodent species were identified. These region-specific
libraries and the unique sequence microclones from the libraries are useful reagents for (1) isolating hughly polymorphic
microsatellite markers for refined linkage analysis, (2) identifying corresponding YAC, BAC or other clones with large inserts
for contig assembly and high resolution physical mapping, (3) isolating cDNA clones from the dissected region, and (4) convenient
sequencing of the microclones to prepare high density markers and sequence-tagged sites (STSs). Such applications have been
demonstrated in a series of similarly constructed microdissection libraries from other regions of the human genome. 相似文献
40.
Actions of some anions on electrical properties and mechanical threshold of frog twitch muscle 总被引:9,自引:1,他引:9
1. Using two micro-electrodes in a point-voltage clamp technique, the effects of the lyotropic anions, NO(3) (-), Br(-), I(-), SCN(-), and CH(3)SO(4) (-), and of SO(4) (2-) on the mechanical threshold and electrical properties of frog sartorius muscle were studied.2. In chloride Ringer solution the spike threshold was -59 mV, mechanical threshold -48 mV, and the threshold for delayed rectification of the total current at about 100 msec -52 mV.3. When Cl(-) was replaced by one of the lyotropic anions, the effective resistance determined at -100 mV tended to increase. But, because of the variability of the effective resistance in individual fibres, most lyotropic anions did not cause a statistically significant increase in the effective resistance. Only I(-) and SO(4) (2-) significantly increased the effective resistance.4. Most lyotropic anions had no significant effect on the spike threshold; I(-), at 58 mM, lowered it slightly. Sulphate raised the threshold.5. Tetrodotoxin (0.1 mug/ml.) abolished the spikes, but did not affect the mechanical and delayed rectification thresholds. It was, therefore, used to pre-treat all preparations for determining these thresholds.6. All lyotropic anions lowered the mechanical and the delayed rectification thresholds, the order of effectiveness being approximately SCN(-) > I(-) > NO(3) (-) > CH(3)SO(4) (-) > Br(-). As in Cl(-) Ringer, the two thresholds lay very close together in every case. Sulphate raised slightly both the mechanical and delayed rectification thresholds, again in close parallel.7. This close agreement of the mechanical and delayed rectification thresholds is not caused by movement artifact, because in fibres in which visible contractions were eliminated with hypertonic solutions the delayed rectification thresholds were the same as those in contracting fibres.8. In spite of the close agreement, reasons are given to doubt a direct causal relationship between the mechanical and delayed rectification thresholds.9. Nitrate apparently had little effect on the rate of inactivation of the outward current, or on the relation between steady-state inactivation and membrane potential. 相似文献