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991.
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993.
Joensuu T Kuronen M Alakurtti K Tegelberg S Hakala P Aalto A Huopaniemi L Aula N Michellucci R Eriksson K Lehesjoki AE 《European journal of human genetics : EJHG》2007,15(2):185-193
Progressive myoclonus epilepsy of Unverricht-Lundborg type (EPM1) is an autosomal recessive neurodegenerative disorder caused by mutations in the cystatin B gene (CSTB) that encodes an inhibitor of several lysosomal cathepsins. An unstable expansion of a dodecamer repeat in the CSTB promoter accounts for the majority of EPM1 disease alleles worldwide. We here describe a novel PCR protocol for detection of the dodecamer repeat expansion. We describe two novel EPM1-associated mutations, c.149G > A leading to the p.G50E missense change and an intronic 18-bp deletion (c.168+1_18del), which affects splicing of CSTB. The p.G50E mutation that affects the conserved QVVAG amino acid sequence critical for cathepsin binding fails to associate with lysosomes. This further supports the previously implicated physiological importance of the CSTB-lysosome association. Expression of CSTB mRNA and protein was markedly reduced in lymphoblastoid cells of the patients irrespective of the mutation type. Patients homozygous for the dodecamer expansion mutation showed 5-10% expression compared to controls. By combining database searches with RT-PCR we identified several alternatively spliced CSTB isoforms. One of these, CSTB2, was also present in mouse and was analyzed in more detail. In real-time PCR quantification, CSTB2 expression was less than 5% of total CSTB expression in all human adult and fetal tissues analyzed. In patients homozygous for the minisatellite mutation, the level of CSTB2 was reduced similarly to that of CSTB implicating regulation from the same promoter. The physiological significance of CSTB2 remains to be determined. 相似文献
994.
Hou M Andersson M Eksborg S Söder O Jahnukainen K 《Human reproduction (Oxford, England)》2007,22(7):1899-1906
BACKGROUND: Xeno-grafting of testicular tissue may allow viable gamete maturation. This would be beneficial for prepubertal cancer patients in that it may allow restoration of fertility without the risk of a cancer relapse. However it is unknown whether cancer cells in the testicular graft can transmit the malignancy into the host animal and also if gametes can be retrieved from testicular grafts that are contaminated with malignant cells. METHODS: Rat T-cell leukemia was employed as the source of leukemic lymphoblasts and testicular tissue. This was injected i.p. (lymphoblasts) or grafted s.c. (fresh or cryopreserved testicular tissue) into the back skin of intact nude mice. To simulate clinical autografting, testicular tissue was also transplanted into healthy piebald variegated (PVG) rats. RESULTS: 50-70% of the mice, receiving 200 or 6000 leukemic lymphoblasts, developed terminal leukemia. All mice, grafted with either fresh or cryopreserved testicular tissue from leukemic donor, developed generalized leukemia and/or local tumors. All syngenic PVG rats, treated in the same manner, died of generalized leukemia. In all of the retrieved leukemic grafts, rat spermatogenesis was destroyed and only leukemic infiltration was detected. CONCLUSIONS: Grafting testicular tissue contaminated with leukemic cells led to tumor growth at the injection site without potential to differentiate germline stem cells into gametes. Xenografting could provide a novel functional strategy for simultaneous detection of malignant cell contamination and spermatogonial potential in testicular xenografts collected for fertility preservation. 相似文献
995.
Pauliina Mattila-Holappa Matti Joensuu Kirsi Ahola Teija Kivekäs Mika Kivimäki Aki Koskinen 《Scandinavian journal of occupational therapy》2018,25(3):213-222
AbstractBackround: Little is known about treatment and rehabilitation received and planned among young adults with work disability due to a mental disorder.Aims: To examine the implemented psychotherapeutic and vocational interventions and treatment plans among young adults with work disability due to a mental disorder.Material and methods: Data were collected from medical records of young Finnish adults aged 18–34 with a long-term work disability history due to a mental disorder (N?=?1163). The participant characteristics associated with four types of interventions were analyzed using log-binomial regression analysis.Results: In total, 34% had participated in a psychotherapeutic intervention. Of the non-students, 26% had participated in vocational intervention. For 46% of the non-students, neither type of intervention was planned. Both implemented and planned psychotherapeutic interventions were associated with female sex, high education, attachment to employment, and absence of substance abuse. Low education and childhood adversity were associated with implemented vocational interventions and absence of substance abuse with planned vocational interventions.Conclusion and significance: There is an unmet need for psychotherapeutic interventions among men, among those with lower socio-economic status, and among those with poor attachment to labor market. In addition, there is a lack of vocational interventions for those with high education. People with substance abuse are largely excluded from both types of interventions. 相似文献
996.
Suvi Raitakari PhD Riikka Haahtela PhD Kirsi Juhila PhD 《Health & social care in the community》2016,24(5):e53-e62
Integration – and its synonym inclusion – is emphasised in the western welfare states and in the European Union in particular. Integration is also a central topic in the social sciences and in current mental health and homelessness research and practice. As mental healthcare has shifted from psychiatric hospitals to the community, it has inevitably become involved with housing and integration issues. This article explores how community integration is understood and tackled in mental health floating support services (FSSs) and, more precisely, in service user–practitioner home visit interaction. The aim, through shedding light on how the idea of integration is present and discussed in front‐line mental health practices, is to offer a ‘template’ on how we might, in a systematic and reflective way, develop community integration research and practice. The analysis is based on ethnomethodological and micro‐sociological interaction research. The research settings are two FSSs located in a large Finnish city. The data contain 24 audio‐recorded and transcribed home visits conducted in 2011 and 2012 with 16 different service users. The study shows how the participants in service user–practitioner interaction give meaning to community integration and make decisions about how it should (or should not) be enhanced in each individual case. This activity is called community integration work in action. Community integration work in action is based on various dimensions of integration: getting out of the house, participating in group activities and getting along with those involved in one's life and working life. Additionally, the analysis demonstrates how community integration work is accomplished by discursive devices (resistance, positioning, excuses and justifications, delicacy and advice‐giving). The article concludes that community integration is about interaction: it is not only service users' individual challenge but also a social challenge, our challenge. 相似文献
997.
The 3' non-translated regions (NTRs) of mRNAs of eukaryotes and their viruses often contain translational enhancers (TEs). Blackcurrant reversion nepovirus (BRV) has a genome composed of two uncapped polyadenylated RNAs with very long 3' NTRs, nucleotide sequences of which are very conserved between different BRV isolates. In this work, we studied a role of the RNA2 3' NTR in translation, using mutagenesis of the firefly luciferase reporter mRNA, in protoplasts of Nicotiana benthamiana. The RNA2 3' NTR was found to contain a cap-independent TE (3' CITE), which must base pair with the 5' NTR to facilitate translation. The BRV 3' CITE and poly(A) tail provided a major contribution to translational efficiency, with less input from other 3' NTR parts. The BRV 3' CITE does not share similarity in nucleotide sequence and secondary structure with other viruses and thus represents a new class of 3' CITE. 相似文献
998.
Sonkoly E Muller A Lauerma AI Pivarcsi A Soto H Kemeny L Alenius H Dieu-Nosjean MC Meller S Rieker J Steinhoff M Hoffmann TK Ruzicka T Zlotnik A Homey B 《The Journal of allergy and clinical immunology》2006,117(2):411-417
BACKGROUND: IL-31 is a novel T-cell-derived cytokine that induces severe pruritus and dermatitis in transgenic mice, and signals through a heterodimeric receptor composed of IL-31 receptor A and oncostatin M receptor. OBJECTIVE: To investigate the role of human IL-31 in pruritic and nonpruritic inflammatory skin diseases. METHODS: The expression of IL-31 was analyzed by quantitative real-time PCR in skin samples of healthy individuals and patients with chronic inflammatory skin diseases. Moreover, IL-31 expression was analyzed in nonlesional skin of atopic dermatitis patients after allergen or superantigen exposure, as well as in stimulated leukocytes. The tissue distribution of the IL-31 receptor heterodimer was investigated by DNA microarray analysis. RESULTS: IL-31 was significantly overexpressed in pruritic atopic compared with nonpruritic psoriatic skin inflammation. Highest IL-31 levels were detected in prurigo nodularis, one of the most pruritic forms of chronic skin inflammation. In vivo, staphylococcal superantigen rapidly induced IL-31 expression in atopic individuals. In vitro, staphylococcal enterotoxin B but not viruses or T(H)1 and T(H)2 cytokines induced IL-31 in leukocytes. In patients with atopic dermatitis, activated leukocytes expressed significantly higher IL-31 levels compared with control subjects. IL-31 receptor A showed most abundant expression in dorsal root ganglia representing the site where the cell bodies of cutaneous sensory neurons reside. CONCLUSION: Our findings provide a new link among staphylococcal colonization, subsequent T-cell recruitment/activation, and pruritus induction in patients with atopic dermatitis. Taken together, these findings show that IL-31 may represent a novel target for antipruritic drug development. 相似文献
999.
Kirsi Karvala Elina Toskala Ritva Luukkonen Sanna Lappalainen Jukka Uitti Henrik Nordman 《International archives of occupational and environmental health》2010,83(8):855-865
Objective
Damp and moldy indoor environments aggravate pre-existing asthma. Recent meta-analyses suggest that exposure to such environments may also induce new-onset asthma. We assessed the probability of molds being the cause of asthma in a patient series examined because of respiratory symptoms in relation to workplace dampness and molds. 相似文献1000.
Glucuronic Acid Epimerase (GLCE) Variant rs3865014 (A>G) Is Associated with BMI,Blood Hemoglobin,Hypertension, and Cerebrovascular Events,the TAMRISK Study 下载免费PDF全文
Tarja Kunnas Tiina Solakivi Kirsi Määttä Seppo T. Nikkari 《Annals of human genetics》2016,80(6):332-335
Heparan sulfate proteoglycans modulate many physiological systems, and genes responsible for proteoglycan assembly and disassembly may affect their interaction. We sought to determine whether polymorphisms of the glucuronic acid epimerase (GLCE) rs3865014 and sulfatase‐2 (SULF2) rs2281279, genes coding for enzymes participating in heparan sulfate side chain activity, associate with hypertension, selected cardiometabolic risk factors and cardiovascular events in the Tampere adult population cardiovascular risk study. A Finnish cohort of 339 subjects with diagnosed hypertension and 441 controls was analyzed. Samples were genotyped for GLCE rs3865014 (A>G) and SULF2 rs2281279 (T>C) polymorphisms using competitive allele‐specific PCR (KASP) technique. Prevalence of ischemic heart diseases (I20–I25) and incidence of cerebrovascular diseases (I60–I69) and transient cerebral ischemic attacks (TIA) (G45) were followed up until the subjects were on the average 60 years old. GLCE rs3865014 G allele showed negative association with hypertension (p = 0.022), waist circumference (p = 0.032), BMI (p = 0.048), and positive association with hemoglobin (p = 0.029), low‐density lipoprotein cholesterol (p = 0.031), and frequency of cerebrovascular events (p = 0.011). SULF2 rs2281279 showed no association with the studied parameters. The GLCE gene polymorphism rs3865014 appears to have biological relevance in human pathophysiology. 相似文献