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1.
Merkel cell polyomavirus (MCPyV), human polyomaviruses 6 (HPyV6) and 7 (HPyV7) are novel human polyomaviruses. This study investigated their detection rates and DNA loads in various skin cancers from Japanese patients. MCPyV, HPyV6 and HPyV7 were detected in 22.2%, 3.2% and 1.6% of squamous cell carcinomas, 18.0%, 2.0% and 4.0% of basal cell carcinomas, and 19.1%, 4.3% and 4.3% of melanomas, respectively. Quantitative real‐time polymerase chain reaction showed that their DNA loads were low. These findings provide the first evidence of the prevalence of HPyV6 and HPyV7 in skin cancers in Asia. Nucleotide differences were found in the large T‐sequenced region between Japanese and North American isolates: a nucleotide substitution of A to G for HPyV6; and a nucleotide substitution of T to C and the insertion of a gap for HPyV7. This suggested that two genotypes of HPyV6 and HPyV7 would be present and associated with geographical origin.  相似文献   
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Primary localized cutaneous nodular amyloidosis (PLCNA) is a rare subtype of localized cutaneous amyloidosis and can be associated with various connective tissue disorders. It can be difficult to treat and past therapies include surgical excision, dermabrasion, electrodessication and curettage, cryotherapy and laser therapy. We present a case of a middle‐aged woman with PLCNA associated with CREST (calcinosis, Raynaud phenomenon, oesophageal motility disorders, sclerodactyly and telangiectasia) syndrome and Sjögren's syndrome responding to cyclophosphamide with no new amyloid deposits and resolution of skin ulceration after many years of resistance to drug therapy. It is important to monitor these patients for progression into systemic amyloidosis.  相似文献   
4.
This case study reports the clinical, skin biopsy and molecular findings in a 56‐year‐old Filipino man with the autosomal recessive ectodermal dysplasia disorder, Schöpf‐Schulz‐Passarge syndrome, the precise nature of which was established only after reading of a similar case in this journal. In addition to the late diagnosis, successful clinical management of his acral hyperkeratosis and ulceration has been difficult, with oral retinoids exacerbating the skin fragility.  相似文献   
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To explore a novel therapy against Parkinson's disease through enhancement of α7 nicotinic acetylcholine receptor (nAChR), we evaluated the neuroprotective effects of 3‐[(2,4‐dimethoxy)benzylidene]‐anabaseine dihydrochloride (DMXBA; GTS‐21), a functionally selective α7 nAChR agonist, in a rat 6‐hydroxydopamine (6‐OHDA)‐induced hemiparkinsonian model. Microinjection of 6‐OHDA into the nigrostriatal pathway of rats destroys dopaminergic neurons selectively. DMXBA dose dependently inhibited methamphetamine‐stimulated rotational behavior and dopaminergic neuronal loss induced by 6‐OHDA. The protective effects were abolished by methyllycaconitine citrate salt hydrate, an α7 nAChR antagonist. Immunohistochemical study confirmed abundant α7 nAChR expression in the cytoplasm of dopaminergic neurons. These results indicate that DMXBA prevented 6‐OHDA‐induced dopaminergic neuronal loss through stimulating α7 nAChR in dopaminergic neurons. Injection of 6‐OHDA elevated immunoreactivities to glial markers such as ionized calcium binding adaptor molecule 1, CD68, and glial fibrillary acidic protein in the substantia nigra pars compacta of rats. In contrast, these immunoreactivities were markedly inhibited by comicroinjection of DMXBA. Microglia also expressed α7 nAChR in both resting and activated states. Hence, we hypothesize that DMXBA simultaneously affects microglia and dopaminergic neurons and that both actions lead to dopaminergic neuroprotection. The findings that DMXBA attenuates 6‐OHDA‐induced dopaminergic neurodegeneration and glial activation in a rat model of Parkinson's disease raisethe possibility that DMXBA could be a novel therapeutic compound to prevent Parkinson's disease development. © 2012 Wiley Periodicals, Inc.  相似文献   
7.
Lack of regeneration in the adult central nervous system (CNS) is a major hurdle that limits recovery from neurological ailments. Although accumulating research suggests the possibility of axon regeneration by targeting intrinsic signaling mechanisms, it remains a matter of controversy whether functional recovery can be achieved by manipulating aspects of molecular signaling. Recent studies have shown that granulocyte macrophage colony‐stimulating factor (GM‐CSF) may be an effective means of targeting repair following CNS injury; how this molecule is able to produce this effect is not known. Indeed, GM‐CSF has been shown to promote neuronal survival, potentially through activation of as yet unknown cytokine‐dependent signals and potentially through regulation of antiapoptotic mechanisms. It is well established that the loss of intrinsic regenerative ability is highly correlated with development of CNS neurons. We therefore designed experiments, using a well‐established in vitro retinal ganglion cell (RGC) culture system, to evaluate the effect of GM‐CSF on axon growth and cell survival and define possible mechanisms involved in GM‐CSF‐mediated effects in vitro. Several developmental stages were evaluated, with particular focus placed on stages at which axon growth is known to be significantly diminished. Our results reveal that GM‐CSF not only promotes axon growth in postnatal RGCs but also enhances cell survival through a mammalian target of rapamycin (mTOR)‐dependent mechanism. © 2013 Wiley Periodicals, Inc.  相似文献   
8.
Balance impairment is a principal symptom of cerebellar disease, but is poorly understood partly because subjects with heterogenous cerebellar and extracerebellar lesions have often been studied. Spinocerebellar ataxia type 6 (SCA6) provides an opportunity to understand balance dysfunction associated with a relatively homogenous cerebellar lesion. This study investigated stance instability in SCA6 and how it is affected by varying stance width. Body sway, as well as its directional preponderance and distribution across joints, was measured three‐dimensionally in 17 SCA6 and 17 matched healthy control subjects. Subjects stood for 40 seconds on a stable surface with their eyes open and feet positioned at various stance widths (32, 16, 8, 4, and 0 cm). SCA6 subjects swayed faster than controls at every stance width. Decreasing the stance width produced a disproportionate increase in sway speed in SCA6 subjects, compared to controls. Directional preponderance of sway was dependent on stance width, but did not differ between groups. Joint instability was increased by reducing stance width in both groups, but there was greater instability of the ankle joint in the roll plane in the SCA6 group. Measures of global instability correlated strongly with disease severity measured with the Scale for the Assessment and Rating of Ataxia (r = 0.79). The sway characteristics suggest a disruption of sensorimotor processing for balance control in SCA6. The correlation with disease severity implies that balance impairment is a feature of progression of SCA6 clinical syndrome. With stance width standardized, the instability measures employed could provide sensitive, continuous outcome measures of longitudinal or therapeutic change. © 2012 Movement Disorder Society  相似文献   
9.
Tetrabenazine is effective in the treatment of the chorea associated with Huntington disease and other hyperkinetic movement disorders. Following oral administration, tetrabenazine is hepatically transformed into 2 active metabolites that are CYP2D6 substrates. There are 4 CYP2D6 genotypes: poor metabolizers, intermediate metabolizers, extensive metabolizers, and ultrarapid metabolizers. CYP2D6 genotyping was performed on sequential subjects treated with tetrabenazine, but results were not known at the time of titration. Duration of titration to a stable dose, total daily dose, response rating scores, and adverse events were retrospectively collected and subsequently analyzed. Of 127 patients, the majority (n = 100) were categorized as extensive metabolizers, 14 as intermediate metabolizers, 11 as poor metabolizers, and 2 as ultrarapid metabolizers. Ultrarapid metabolizer patients needed a longer titration (8 vs 3.3, 4.4, and 3 weeks, respectively; P < .01) to achieve optimal benefit and required a higher average daily dose than the other patients, but this difference did not reach statistical significance. The treatment response was less robust in the intermediate metabolizer group when compared with the extensive metabolizer patients (P = .013), but there were no statistically significant differences between the various groups with regard to adverse effects. Our findings demonstrate that, aside from the need for a longer titration in the ultrarapid metabolizers, there are no distinguishing features of patients with various CYP2D6 genotypes, and therefore the current recommendation to systematically genotype all patients prescribed more than 50 mg/day of tetrabenazine should be reconsidered. © 2012 Movement Disorder Society  相似文献   
10.
To evaluate the hypothesis that functionally over‐expressing alleles of the serotonin transporter (SERT) gene (solute carrier family 6, member 4, SLC6A4) are present in Tourette's disorder (TD), just as we previously observed in obsessive compulsive disorder (OCD), we evaluated TD probands (N = 151) and controls (N = 858). We genotyped the refined SERT‐linked polymorphic region 5‐HTTLPR/rs25531 and the associated rs25532 variant in the SLC6A4 promoter plus the rare coding variant SERT isoleucine‐to‐valine at position 425 (I425V). The higher expressing 5‐HTTLPR/rs25531 LA allele was more prevalent in TD probands than in controls (χ2 = 5.75; P = 0.017; odds ratio [OR], 1.35); and, in a secondary analysis, surprisingly, it was significantly more frequent in probands who had TD alone than in those who had TD plus OCD (Fisher's exact test; P = 0.0006; OR, 2.29). Likewise, the higher expressing LAC haplotype (5‐HTTLPR/rs25531/rs25532) was more frequent in TD probands than in controls (P = 0.024; OR, 1.33) and also in the TD alone group versus the TD plus OCD group (P = 0.0013; OR, 2.14). Furthermore, the rare gain‐of‐function SERT I425V variant was observed in 3 male siblings with TD and/or OCD and in their father. Thus, the cumulative count of SERT I425V becomes 1.57% in OCD/TD spectrum conditions versus 0.15% in controls, with a recalculated, family‐adjusted significance of χ2 = 15.03 (P < 0.0001; OR, 9.0; total worldwide genotyped, 2914). This report provides a unique combination of common and rare variants in one gene in TD, all of which are associated with SERT gain of function. Thus, altered SERT activity represents a potential contributor to serotonergic abnormalities in TD. The present results call for replication in a similarly intensively evaluated sample. © 2013 Movement Disorder Society  相似文献   
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