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71.
Scand J Caring Sci; 2012; 26; 113–122
Self‐care ability among home‐dwelling older people in rural areas in southern Norway Introduction: The growing number of older people is assumed to represent many challenges in the future. Self‐care ability is a crucial health resource in older people and may be a decisive factor for older people managing daily life in their own homes. Studies have shown that self‐care ability is closely related to perceived health, sense of coherence and nutritional risk. Aim: The aim of this study was to describe self‐care ability among home‐dwelling older individuals living in rural areas in southern Norway and to relate the results to general living conditions, sense of coherence, screened nutritional state, perceived health, mental health and perceived life situation. Methods: A cross‐sectional survey was carried out in rural areas in five counties in 2010. A mailed questionnaire, containing background variables, health‐related questions and five instruments, was sent to a randomly selected sample of 3017 older people (65+ years), and 1050 respondents were included in the study. Data were analysed with statistical methods. Results: A total of 780 persons were found to have higher self‐care ability and 240 to have lower self‐care ability using the Self‐care Ability Scale for the Elderly. Self‐care ability was found to be closely related to health‐related issues, self‐care agency, sense of coherence, nutritional state and mental health, former profession, and type of dwelling. Predictors for high self‐care ability were to have higher self‐care agency, not receiving family help, having low risk for undernutrition, not perceiving helplessness, being able to prepare food, being active and having lower age. Conclusions: When self‐care ability is reduced in older people, caregivers have to be aware about how this can be expressed and also be aware of their responsibility for identifying and mapping needs for appropriate support and help, and preventing unnecessary and unwanted dependency.  相似文献   
72.
OBJECTIVE: In postmenopausal rheumatoid arthritis (RA), both estrogen deficiency and the inflammatory disease contribute to the development of generalized osteoporosis. Hormone replacement therapy (HRT) with estradiol preserves bone mineral density (BMD) and ameliorates arthritis, but long-term therapy is no longer an option due to significant side effects. We therefore used a mouse model of human RA to test the hypothesis that a selective estrogen receptor modulator (SERM), the raloxifene analog LY117018, could be beneficial in the treatment of both arthritis and osteoporosis. METHODS: Female DBA/1 mice were ovariectomized and arthritis was induced with collagen immunization. Mice received an injection of raloxifene, estradiol, or vehicle control, administered prophylactically or therapeutically, and thereafter the clinical arthritis score was evaluated continuously. At termination, BMD was analyzed with peripheral quantitative computed tomography. Paws were collected for histology, and sera were analyzed for cytokines and markers of bone and cartilage turnover. Levels of cytokine messenger RNA (mRNA) were investigated with real-time polymerase chain reaction. RESULTS: Treatment with raloxifene dramatically decreased the frequency and severity of arthritis. Effective preservation of bone and cartilage was seen in raloxifene-exposed mice, as demonstrated by increased BMD and decreased serum levels of cartilage oligomeric matrix protein in the raloxifene-treated mice compared with controls. Decreased levels of mRNA for both tumor necrosis factor alpha and RANKL in spleen cells from raloxifene-treated arthritic mice indicated an immunosuppressive action of this SERM. CONCLUSION: In a well-established model of postmenopausal RA, the raloxifene analog LY117018 potently inhibits the progression of arthritis and the associated development of osteoporosis, both in a prophylactic and in a therapeutic regimen. Since long-term HRT has been associated with significant side effects, raloxifene may be a useful adjuvant treatment for postmenopausal RA.  相似文献   
73.
Highly exposed persistently seronegative (HEPS) individuals have previously been shown to mount HIV-1-specific humoral and cellular immune responses in the mucosa, despite their uninfected status. It is thus possible that HEPS individuals are protected from HIV-1 infection at the mucosal level. Recent work supports the hypothesis that dendritic cells are involved in the establishment of a mucosal HIV-1 infection as well as the dissemination to other target cells. However, no previous study has investigated if samples collected from HEPS individuals have the capacity to prevent HIV-1 infection in the presence of dendritic cells in vitro. We therefore established an assay that measures HIV-1 neutralization in cocultures of HIV-1-exposed dendritic cells (DC) and PBMC. Plasma and cervicovaginal lavage (CVL) samples from HIV-1-infected patients and HEPS individuals, enrolled in a well-characterized sex worker cohort in Kenya, were evaluated. Most plasma and CVL samples of HIV-1-infected patients neutralized HIV-1 in the DC/PBMC cocultures. Neither plasma nor CVL samples of most HEPS individuals had this capacity. However, they readily neutralized HIV-1 infection of PBMC alone. This may suggest that protection against HIV-1 infection in HEPS individuals occurs prior to interaction between HIV-1-exposed DC and other target cells.  相似文献   
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75.
BACKGROUND: Patients' involvement in their healthcare has been associated with improved treatment outcomes in chronic illness. Less is known about the affects of patient involvement on the outcomes of acute illness, such as myocardial infarction. A better understanding of patients' views and behaviour during hospitalization might improve clinical practice and enhance patient involvement. AIM: The aim of this study was to develop and evaluate a questionnaire for measuring patients' perceptions of their involvement during hospitalization for myocardial infarction care. METHODS: Focus groups with myocardial infarction patients provided the basis for the construction of the questionnaire. Questionnaire validity and reliability were evaluated in a small pilot study and a larger cross-sectional study among myocardial infarction patients at eleven Swedish hospitals. RESULTS: The questionnaire demonstrated good validity and reliability, with six factors measuring patient views and behaviour regarding involvement. CONCLUSION: The questionnaire appears to be a useful tool for evaluating the perceptions and behaviour of patients regarding patient involvement in myocardial infarction care. Use of this questionnaire may provide insight regarding areas of patient-staff interaction that need improvement. Pinpointing such areas may lead to improved patient involvement, satisfaction with care, and treatment outcomes.  相似文献   
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77.
The zebrafish infected with Mycobacterium marinum (M. marinum) is an attractive tuberculosis disease model, showing similar pathogenesis to Mycobacterium tuberculosis (M. tuberculosis) infections in humans. To translate pharmacological findings from this disease model to higher vertebrates, a quantitative understanding of the natural growth of M. marinum in comparison to the natural growth of M. tuberculosis is essential. Here, the natural growth of two strains of M. marinum, E11 and MUSA, is studied over an extended period using an established model‐based approach, the multistate tuberculosis pharmacometric (MTP) model, for comparison to that of M. tuberculosis. Poikilotherm‐derived strain E11 and human‐derived strain MUSA were grown undisturbed up to 221 days and viability of cultures (colony forming unit (CFU)/mL) was determined by plating at different time points. Nonlinear mixed effects modeling using the MTP model quantified the bacterial growth, the transfer among fast, slow, and non‐multiplying states, and the inoculi. Both strains showed initial logistic growth, reaching a maximum after 20–25 days for E11 and MUSA, respectively, followed by a decrease to a new plateau. Natural growth of both E11 and MUSA was best described with Gompertz growth functions. For E11, the inoculum was best described in the slow‐multiplying state, for MUSA in the fast‐multiplying state. Natural growth of E11 was most similar to that of M. tuberculosis, whereas MUSA showed more aggressive growth behavior. Characterization of natural growth of M. marinum and quantitative comparison with M. tuberculosis brings the zebrafish tuberculosis disease model closer to the quantitative translational pipeline of antituberculosis drug development.

Study Highlights
  • WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC?
☑ Zebrafish infected with Mycobacterium marinum (M. marinum), a close relative to Mycobacterium tuberculosis (M. tuberculosis), show similar pathogenesis to M. tuberculosis infections in humans, making this a frequently used disease model to study tuberculosis pathology and antituberculosis pharmacology.
  • WHAT QUESTION DID THIS STUDY ADDRESS?
☑ The natural growth of two M. marinum strains (E11 and MUSA) is characterized over a period of > 200 days and quantitatively compared with the natural growth of M. tuberculosis.
  • WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE?
☑ The poikilotherm‐derived strain (E11) showed most similar growth parameters and behavior to those of M. tuberculosis. The human‐derived strain (MUSA) showed more aggressive growth. This suggests that studies with E11 are more predictive of antibiotic effects on M. tuberculosis.
  • HOW MIGHT THIS CHANGE CLINICAL PHARMACOLOGY OR TRANSLATIONAL SCIENCE?
☑ Quantitative knowledge on the similarities and differences in natural growth between M. marinum strains and M. tuberculosis is essential for the translation of pharmacological findings on antituberculosis drugs between the zebrafish and higher vertebrates, including humans.

The zebrafish (Danio rerio) is an increasingly utilized disease model organism to study tuberculosis. 1 , 2 Infections of zebrafish embryos with Mycobacterium marinum (M. marinum), a close relative of Mycobacterium tuberculosis (M. tuberculosis), 3 show similar pathogenesis to M. tuberculosis infection in humans. 4 The zebrafish as a disease model organism has several advantages. In contrast to experiments in higher vertebrates, like rodents, experiments with the zebrafish and specifically the zebrafish embryos and larvae are less time‐consuming and resource‐consuming. This is because of their high fecundity, small size enabling experiments in microtiter plates with high throughput potential, ease of noninvasive imaging due to its transparency, and limited ethical constraints. 5 , 6 , 7 As a whole vertebrate organism, it contains all relevant organ systems, including the immune response, which is an advantage over in vitro experiments. In tuberculosis research, this is especially relevant, as it has been shown that M. tuberculosis responds differently to treatment intracellularly inside macrophages, in comparison to standard (extracellular) in vitro experiments without macrophages. 8 , 9 Moreover, the interaction among pathogen, immune response, and treatment might be more relevant to study in the zebrafish, as it shows granuloma formation upon infection, 10 which is not observed in the mouse, the standard preclinical organism in tuberculosis research. 11 Translation of pharmacological findings from zebrafish embryos to higher vertebrates, including humans, requires a quantitative understanding of similarities and differences in pathophysiology between infecting mycobacteria. This forms the basis for a translational framework in drug development. One proposed model‐based drug development approach for tuberculosis is the multistate tuberculosis pharmacometric (MTP) model. 12 This model distinguishes three states of multiplication for mycobacteria (i.e., fast, slow, and non‐multiplying states) and characterizes growth rates and transfer rates among these states in the absence and in the presence of drugs, to better understand and translate drug effects. The MTP model has been successfully used in translation of pharmacological findings of M. tuberculosis treatment in vitro, 12 to mice 13 and humans. 14 , 15 , 16 , 17 , 18 To include the zebrafish in the translational pipeline for tuberculosis drug development, it is necessary to study the natural growth of M. marinum and quantitatively compare this to M. tuberculosis.Here, the natural growth of M. marinum was studied over an extended period in two strains, one poikilotherm‐derived (E11) and one human‐derived (MUSA) strain. To facilitate a quantitative comparison to natural growth of M. tuberculosis and thereby assess the translational potential of pharmacological findings between species, the natural growth was characterized using the MTP model. 12   相似文献   
78.
Singbrant S  Moody JL  Blank U  Karlsson G  Umans L  Zwijsen A  Karlsson S 《Blood》2006,108(12):3707-3712
Smad5 is known to transduce intracellular signals from bone morphogenetic proteins (BMPs), which belong to the transforming growth factor-beta (TGF-beta) superfamily and are involved in the regulation of hematopoiesis. Recent findings suggest that BMP4 stimulates proliferation of human primitive hematopoietic progenitors in vitro, while early progenitors from mice deficient in Smad5 display increased self-renewal capacity in murine embryonic hematopoiesis. Here, we evaluate the role of Smad5 in the regulation of hematopoietic stem cell (HSC) fate decisions in adult mice by using an inducible MxCre-mediated conditional knockout model. Surprisingly, analysis of induced animals revealed unperturbed cell numbers and lineage distribution in peripheral blood (PB), bone marrow (BM), and the spleen. Furthermore, phenotypic characterization of the stem cell compartment revealed normal numbers of primitive lin(-)Sca-1(+)c-Kit(+) (LSK) cells in Smad5(-)(/)(-) BM. When transplanted in a competitive fashion into lethally irradiated primary and secondary recipients, Smad5-deficient BM cells competed normally with wild-type (wt) cells, were able to provide long-term reconstitution for the hosts, and displayed normal lineage distribution. Taken together, Smad5-deficient HSCs from adult mice show unaltered differentiation, proliferation, and repopulating capacity. Therefore, in contrast to its role in embryonic hematopoiesis, Smad5 is dispensable for hematopoiesis in the adult mouse.  相似文献   
79.
BACKGROUND: Our aim was to determine whether the change in left ventricular (LV) mass in response to antihypertensive treatment could be predicted by multivariate analysis of single nucleotide polymorphisms (SNPs) in candidate genes reflecting pathways likely to be involved in blood pressure control. METHODS: Patients with mild to moderate primary hypertension and LV hypertrophy were randomized in a double-blind fashion to treatment with either the angiotensin II type 1 receptor antagonist irbesartan (n = 48) or the beta1 adrenoreceptor blocker atenolol (n = 49). A microarray-based minisequencing system was used for genotyping 74 SNPs in 25 genes. These genotypes were related to the change in LV mass index by echocardiography, after 12 weeks treatment as monotherapy, using stepwise multiple regression analysis. RESULTS: The blood pressure reductions were similar and significant in both treatment groups. Two SNPs in two separate genes (the angiotensinogen T1198C polymorphism, corresponding to the M235T variant and the apolipoprotein B G10108A polymorphism) for those treated with irbesartan, and the adrenoreceptor alpha2A A1817G for those treated with atenolol, significantly predicted the change in LV mass. The predictive power of these SNPs was independent of the degree of blood pressure reduction. CONCLUSION: SNPs in the angiotensinogen, apolipoprotein B, and the alpha2 adrenoreceptor gene predicted the change in LV mass during antihypertensive therapy. These results illustrate the potential of using microarray-based technology for SNP genotyping in predicting individual drug responses.  相似文献   
80.
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