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A large body of behavioural research has used the cued task‐switching paradigm to characterize the nature of trial‐by‐trial preparatory adjustments that enable fluent task implementation when demands on cognitive flexibility are high. This work reviews the growing number of fMRI studies on the same topic, mostly focusing on the central hypothesis that preparatory adjustments should be indicated by enhanced prefrontal and parietal BOLD activation in task switch when compared with task repeat trials under conditions that enable advance task preparation. The evaluation of this straight‐forward hypothesis reveals surprisingly heterogeneous results regarding both the precise localization and the very existence of switch‐related preparatory activation. Explanations for these inconsistencies are considered on two levels. First, we discuss methodological issues regarding (i) the possible impact of different fMRI‐specific experimental design modifications and (ii) statistical uncertainty in the context of massively multivariate imaging data. Second, we discuss explanations related to the multidimensional nature of task preparation itself. Specifically, the precise localization and the size of switch‐related preparatory activation might depend on the differential interplay of hierarchical control via abstract task goals and attentional versus action‐directed preparatory processes. We argue that different preparatory modes can be adopted relying either on advance goal activation alone or on the advance resolution of competition within action sets or attentional sets. Importantly, while either mode can result in a reduction of behavioral switch cost, only the latter two are supposed to be associated with enhanced switch versus repeat BOLD activation in prepared trial conditions. Hum Brain Mapp, 2013. © 2011 Wiley Periodicals, Inc.  相似文献   
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Background

The proportion of people in need of care with a migration background and therefore the demand for qualified nursing staff will increase. So far, however, considerations and concepts aiming to improve the care situation (including cultural sensitivity) for people in need of care with a migration background are lacking.

Objective

The following questions are addressed on the basis of care training for relatives with migration background and competence development for health care professionals: What content should the care training/competence development take into account? What are the limits regarding planning and implementation, and what are the suggestions for improvements?

Materials and methods

The development of care training and competence development was based on a needs and resources assessment (in the form of a systematic literature review, an expert workshop, semistructured interviews with relatives with migration background who are providing nursing care). A training manual that has been published includes research results and findings and is applicable to other target groups and settings.

Results and discussion

A transcultural training manual was developed and tested for use in outpatient care. It consists of two parts: training for relatives providing nursing care and competency training for health care specialists. It enables the planning, preparation, and implementation of training courses and includes theoretical background knowledge, practical exercises, and didactic advice. When using the manual, however, the target group should be planned at an early stage and individual needs and resources of course participants should be taken into account.
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BACKGROUND: Peptidome profiling of human urine is a promising tool to identify novel disease-associated biomarkers; however, a wide range of preanalytical variables influence the results of peptidome analysis. Our aim was to develop a standardized protocol for reproducible urine peptidome profiling by means of magnetic bead (MB) separation followed by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry (MS). METHODS: MBs with defined surface functionalities (hydrophobic interaction, cation exchange, and metal ion affinity) were used for peptide fractionation of urine. Mass accuracy and imprecision were calculated for 9 characteristic mass signals (M(r), 1000-10,000). Exogenous variables (instrument performance, urine sampling/storage conditions, freezing conditions, and freeze-thaw cycles) and endogenous variables (pH, urine salt and protein concentrations, and blood and bacteria interferences) were investigated with urine samples from 10 male and 10 female volunteers. RESULTS: We detected 427 different mass signals in the urine of healthy donors. Within- and between-day imprecision in relative signal intensities ranged from 1% to 14% and from 4% to 16%, respectively. Weak cation-exchange and metal ion affinity MB preparations required adjustment of the urinary pH to 7. Storage time, storage temperature, the number of freeze-thaw cycles, and bacterial and blood contamination significantly influenced urine peptide patterns. Individual urine peptide patterns differed significantly within and between days. This imprecision was diminished by normalization to a urinary protein content of 3.5 microg. CONCLUSION: This reliable pretreatment protocol allows standardization of preanalytical modalities and facilitates reproducible peptidome profiling of human urine by means of MB separation in combination with MALDI-TOF MS.  相似文献   
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Background

Atopic dermatitis is a chronic and severe pruritic skin disease. Interlukin-31 (IL-31) has been recently demonstrated to be one of the key pruritogens in atopic dermatitis. However, the mechanisms underlying IL-31-induced itching remains unclear. In our previous study, we have shown that thromboxane (TX) A2 is involved in itch-associated responses in mice with atopy-like skin diseases.

Methods

IL-31 was given intradermally into the rostral back of ICR mice and the hind-paw scratching to the injection site were counted. Expression of TX synthase and IL-31 receptors were analyzed using immunohistochemical staining or RT-PCR in mouse skin or primary cultures of mouse keratinocytes. The concentration of TXB2, a metabolite of TXA2, in the skin and the culture medium of primary cultures of mouse keratinocytes was measured using enzyme immunoassay. The concentration of intracellular Ca2+ ions in mouse keratinocytes was measured using the calcium imaging method.

Results

An intradermal injection of IL-31 elicited scratching, an itch-related response, in mice. The scratching was inhibited by TP TXA2 receptor antagonist DCHCH. The distribution of TX synthase and IL-31RA receptor was mainly epidermal keratinocytes in the skin. The primary cultures of keratinocytes expressed the mRNAs of TX synthase and IL-31 receptors. IL-31 increased the concentration of TXB2, which was inhibited by TX synthase inhibitor sodium ozagrel and EGTA, in the skin and the culture medium of primary cultures of keratinocytes. IL-31 increased the concentration of intracellular Ca2+ ions in mouse keratinocytes.

Conclusion

It is suggested that IL-31 elicits itch-associated responses through TXA2 produced from keratinocytes.  相似文献   
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Desmoplastic small round cell tumors (DSRCTs) are highly aggressive sarcomas that most commonly occur intra‐abdominally, and are defined by EWSR1WT1 gene fusion. Intracranial DSRCTs are exceptionally rare with only seven previously reported fusion‐positive cases. Herein, we evaluate the clinical, morphologic, immunohistochemical and molecular features of five additional examples. All patients were male (age range 6–25 years; median 11 years), with four tumors located supratentorially and one within the posterior fossa. The histologic features were highly variable including small cell, embryonal, clear cell, rhabdoid, anaplastic and glioma‐like appearances. A prominent desmoplastic stroma was seen in only two cases. The mitotic index ranged from <1 to 12/10 HPF (median 5). While all tumors showed strong desmin positivity, epithelial markers such as EMA, CAM 5.2 and other keratins were strongly positive in only one, focally positive in two and negative in two cases. EWSR1WT1 gene fusion was present in all cases, with accompanying mutations in the TERT promoter or STAG2 gene in individual cases. Given the significant histologic diversity, in the absence of genetic evaluation these cases could easily be misinterpreted as other entities. Desmin immunostaining is a useful initial screening method for consideration of a DSRCT diagnosis, prompting confirmatory molecular testing. Demonstrating the presence of an EWSR1WT1 fusion provides a definitive diagnosis of DSRCT. Genome‐wide methylation profiles of intracranial DSRCTs matched those of extracranial DSRCTs. Thus, despite the occasionally unusual histologic features and immunoprofile, intracranial DSRCTs likely represent a similar, if not the same, entity as their soft tissue counterpart based on the shared fusion and methylation profiles.  相似文献   
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