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71.
Apotemnophilia, or body integrity image disorder (BIID), is characterised by a feeling of mismatch between the internal feeling of how one's body should be and the physical reality of how it actually is. Patients with this condition have an often overwhelming desire for an amputation- of a specific limb at a specific level. Such patients are not psychotic or delusional, however, they do express an inexplicable emotional abhorrence to the limb they wish removed. It is also known that such patients show a left-sided preponderance for their desired amputation. Often they take drastic action to be rid of the offending limb. Given the left-sided bias, emotional rejection and specificity of desired amputation, we suggest that there are clear similarities to be drawn between BIID and somatoparaphrenia. In this rare condition, which follows a right parietal stroke, the patient rejects (usually) his left arm as "alien". We go on to hypothesis that a dysfunction of the right parietal lobe is also the cause of BIID. We suggest that this leads to an uncoupling of the construct of one's body image in the right parietal lobe from how one's body physically is. This hypothesis would be amenable to testing by response to cold-water vestibular caloric stimulation, which is known to temporarily treat somatoparaphrenia. It could also be investigated using functional brain imaging and skin conductance response. If correct our hypothesis not only suggests why BIID arises, but also, in caloric stimulation a therapeutic avenue for this chronic and essentially untreatable condition. 相似文献
72.
Altschuler EL Altschuler BM Altschuler DL Samber D Ramachandran VS 《Medical hypotheses》2007,69(2):381-382
In the modern society of the printed word dyslexia can be distressing and disabling. Commonly dyslexia manifests as a difficulty reading often caused by confusion or reversal of certain letters such as 'b' and 'd', and 'p' and 'q' and 'g'. Here we suggest that one method of remediation or amelioration is to print letters in color such as a 'b' in blue print, an 'r' in red, 'g' in green and 'p' in pink. Such coloring of letters takes advantage of the well-known association of vision of the color with the color's name--and therefore enunciation of the color's first letter. 相似文献
73.
Identification of neutralizing linear epitopes from the VP1 capsid protein of Enterovirus 71 using synthetic peptides 总被引:1,自引:0,他引:1
Enterovirus 71 (EV71) is the main causative agent of Hand, foot and mouth disease (HFMD) and has been associated with severe neurological diseases resulting in high mortalities. Currently, there is no vaccine available and treatment is limited to palliative care. In this study, antisera were raised in mice against 95 overlapping synthetic peptides spanning the VP1 capsid protein of EV71. Two peptides, SP55 and SP70, containing amino acid 163-177 and 208-222 of VP1, respectively, are capable of eliciting neutralizing antibodies against EV71 in the in vitro microneutralization assay. SP70 was identified to be particularly potent in eliciting a neutralizing antibody titer comparable to that obtained with a whole virion-immune serum. Immunization of mice with either SP55 or SP70 triggered an EV71-specific IgG response as high as that obtained with the whole virion as immunogen. The IgG sub-typing revealed that the neutralizing antibodies elicited by both synthetic peptides are likely belonging to the IgG1 sub-type. Alignment with databases showed that the amino acid residues of SP70 are highly conserved amongst the VP1 sequences of EV71 strains from various sub-genogroups. Altogether, these data indicate that SP70 represents a promising candidate for an effective synthetic peptide-based vaccine against EV71. 相似文献
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Mahmoud El-Daly Mahmoud Saifeddine Koichiro Mihara Rithwik Ramachandran Christopher R Triggle Morley D Hollenberg 《British journal of pharmacology》2014,171(9):2413-2425
Background and Purpose
Because angiotensin-II-mediated porcine coronary artery (PCA) vasoconstriction is blocked by protein tyrosine kinase (PYK) inhibitors, we hypothesized that proteinase-activated receptors (PARs), known to regulate vascular tension, like angiotensin-II, would also cause PCA contractions via PYK-dependent signalling pathways.Experimental Approach
Contractions of intact and endothelium-free isolated PCA rings, stimulated by PAR1/PAR2-activating peptides, angiotensin-II, PGF2α, EGF, PDGF and KCl, were monitored with/without multiple signalling pathway inhibitors, including AG-tyrphostins AG18 (non-specific PYKs), AG1478 (EGF-receptor kinase), AG1296 (PDGF receptor kinase), PP1 (Src kinase), U0126 and PD98059 (MEK/MAPKinase kinase), indomethacin/SC-560/NS-398 (COX-1/2) and L-NAME (NOS).Key Results
AG18 inhibited the contractions induced by all the agonists except KCl, whereas U0126 attenuated contractions induced by PAR1/PAR2 agonists, EGF and angiotensin-II, but not by PGF2α, the COX-produced metabolites of arachidonate and KCl. PP1 only affected the responses to PAR1/PAR2-activating peptides and angiotensin-II. The EGF-kinase inhibitor, AG1478, attenuated contractions initiated by the PARs (PAR2 >> PAR1) and EGF itself, but not by angiotensin-II, PGF2α or KCl. COX-1/2 inhibitors blocked the contractions induced by all the agonists, except KCl and PGF2α.Conclusion and Implications
PAR1/2-mediated contractions of the PCA are dependent on Src and MAPKinase and, in part, involve EGF-receptor-kinase transactivation and the generation of a COX-derived contractile agonist. However, the PYK signalling pathways used by PARs are distinct from each other and from those triggered by angiotensin-II and EGF. These signalling pathways may be therapeutic targets for managing coagulation-proteinase-induced coronary vasospasm. 相似文献78.
Min Yang Anup Ramachandran Hui-Min Yan Benjamin L. Woolbright Bryan L. Copple Peter Fickert Michael Trauner Hartmut Jaeschke 《Toxicology letters》2014
Osteopontin (OPN) is a chemotactic factor which can be cleaved to the pro-inflammatory form by matrix metalloproteinases (MMPs). To test the hypothesis that OPN can modulate inflammatory liver injury during cholestasis, wild-type (WT) C57BL/6 and OPN knockout (OPN-KO) mice underwent bile duct ligation (BDL). OPN-KO mice showed significant reduction in liver injury (plasma ALT and necrosis) and neutrophil recruitment compared with WT animals at 24 h but not 72 h after BDL. In WT mice, a 4-fold increase in hepatic MMP-3 mRNA and elevated MMP activities and cleaved OPN levels were observed in bile. WT mice subjected to BDL in the presence of the MMP inhibitor BB-94 showed reduced liver injury, less neutrophil extravasation and diminished levels of cleaved OPN in bile. Thus, during obstructive cholestasis, OPN released from biliary epithelial cells could be cleaved by MMPs in bile. When the biliary system leaks, cleaved OPN enters the parenchyma and attracts neutrophils. In the absence of OPN, other chemoattractants, e.g. chemokines, mediate a delayed inflammatory response and injury. Taken together, our data suggest that OPN is the pro-inflammatory mediator that initiates the early neutrophil-mediated injury phase during obstructive cholestasis in mice. 相似文献
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Hb A2 and its variant B2 (alpha 2 delta 2(16)(A13)Gly----Arg) were quantitated in the blood of subjects with three different types of beta-thalassemia and with the delta-B2 anomaly in cis or in trans to the beta-thalassemia determinant. In one family, the delta-B2 mutation was in cis to a newly discovered codon 47 (+A) frameshift. The levels of Hbs A2 and B2 were nearly the same and approximately 70% higher than those in simple Hb B2 heterozygotes. In two additional families, the delta-B2 variant was in trans to either a deletional beta-thalassemia (1,393 bp) involving part of the beta-globin gene and part of the beta-globin gene promoter, or to the -88 C----T promoter mutation. In both instances, the Hb B2 level was increased by approximately 80%, but the Hb A2 level was increased by approximately 270% and 200%, respectively. These data indicate two mechanisms that will cause an increase in delta chain production. One is consistent with a general mechanism concerning the relative excess of alpha chains in beta chain deficiencies which will combine with delta chains to form variable levels of Hb A2 dependent on the severity of the beta chain deficiency. The second concerns the loss of beta-globin gene promoter activity, perhaps by an absence of (or decreased) binding of specific protein(s) to this segment of DNA and a concomitant increase in delta-globin gene promoter activity in cis. 相似文献