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91.
We present findings from a qualitative, multisite, multi-method, longitudinal study of parents and their preschool-aged children that explores the intersections of marketing influences in the home and in the larger outside world of children. Findings indicate that preschoolers represent complicated and nuanced “consumers in training” beyond predictions based on their “perceptual stage of development.” Specifically, our data revealed interesting ways in which marketing and consumer culture can foster a number of pro-social consumer outcomes (e.g., charity, gift-giving, financial literacy). We also noted an emerging understanding by preschoolers of the social meanings of goods for identity construction and product evaluation. Finally, through a presentation of an idiographic case, we show how consumer socialization cannot be attributed to one factor such as media but is based on multiple and concurrent factors—parents, siblings, peers, and home environment—that act to moderate, mediate, and provide meaning for marketing messages.  相似文献   
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OBJECTIVERoux-en-Y gastric bypass (RYGB) characteristically enhances postprandial levels of glucagon-like peptide 1 (GLP-1), a mechanism that contributes to its profound glucose-lowering effects. This enhancement is thought to be triggered by bypass of food to the distal small intestine with higher densities of neuroendocrine L-cells. We hypothesized that if this is the predominant mechanism behind the enhanced secretion of GLP-1, a longer intestinal bypass would potentiate the postprandial peak in GLP-1, translating into higher insulin secretion and, thus, additional improvements in glucose tolerance. To investigate this, we conducted a mechanistic study comparing two variants of RYGB that differ in the length of intestinal bypass.RESEARCH DESIGN AND METHODSA total of 53 patients with type 2 diabetes (T2D) and obesity were randomized to either standard limb RYGB (50-cm biliopancreatic limb) or long limb RYGB (150-cm biliopancreatic limb). They underwent measurements of GLP-1 and insulin secretion following a mixed meal and insulin sensitivity using euglycemic hyperinsulinemic clamps at baseline and 2 weeks and at 20% weight loss after surgery.RESULTSBoth groups exhibited enhancement in postprandial GLP-1 secretion and improvements in glycemia compared with baseline. There were no significant differences in postprandial peak concentrations of GLP-1, time to peak, insulin secretion, and insulin sensitivity.CONCLUSIONSThe findings of this study demonstrate that lengthening of the intestinal bypass in RYGB does not affect GLP-1 secretion. Thus, the characteristic enhancement of GLP-1 response after RYGB might not depend on delivery of nutrients to more distal intestinal segments.  相似文献   
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Inflammation Research - The purpose of the review was to synthesize the current literature regarding tetracyclines in the treatment of osteoarthritis. Using multiple databases, a systematic review...  相似文献   
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Gordon  Emma C.  Dunn  Lucy 《Neuroethics》2021,14(3):409-421

Recent discussions of cognitive enhancement often note that drugs and technologies that improve cognitive performance may do so at the risk of “cheapening” our resulting cognitive achievements (e.g., Kass, Life, liberty and the defense of dignity: the challenge for bioethics, Encounter Books, San Francisco, 2004; Agar, Humanity’s end: why we should reject radical enhancement, MIT Press, Cambridge, 2010; Sandel, The case against perfection. Harvard University Press, Cambridge, 2007; Sandel, The case against perfection: what’s wrong with designer children, bionic athletes, and genetic engineering?”. In: Holland (ed) Arguing about bioethics, Routledge, London, 2012; Harris in Bioethics 25:102–111, 2011). While there are several possible responses to this worry, we will highlight what we take to be one of the most promising—one which draws on a recent strand of thinking in social and virtue epistemology to construct an integrationist defence of cognitive enhancement. (e.g., Pritchard in Synthese 175:133–151, 2010; Palermos in Synthese 192:2955–2286, 2015; Clark in Synthese 192:3757–3375, 2015). According to such a line, there is—despite initial appearances to the contrary—no genuine tension between using enhancements to attain our goals and achieving these goals in a valuable way provided the relevant enhancement is appropriately integrated into the agent’s cognitive architecture (in some suitably specified way). In this paper, however, we show that the kind of integration recommended by such views will likely come at a high cost. More specifically, we highlight a dilemma for users of pharmacological cognitive enhancement: they can (1) meet the conditions for cognitive integration (and on this basis attain valuable achievements) at the significant risk of dangerous dependency, or (2) remain free of such dependency while foregoing integration and the valuable achievements that such integration enables. After motivating and clarifying the import of this dilemma, we offer recommendations for how future cognitive enhancement research may offer potential routes for navigating past it.

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Current methods for resolving genetically distinct subclones in tumor samples require somatic mutations to be clustered by allelic frequencies, which are determined by applying a variant calling program to next‐generation sequencing data. Such programs were developed to accurately distinguish true polymorphisms and somatic mutations from the artifactual nonreference alleles introduced during library preparation and sequencing. However, numerous variant callers exist with no clear indication of the best performer for subclonal analysis, in which the accuracy of the assigned variant frequency is as important as correctly indicating whether the variant is present or not. Furthermore, sequencing depth (the number of times that a genomic position is sequenced) affects the ability to detect low‐allelic fraction variants and accurately assign their allele frequencies. We created two synthetic sequencing datasets, and sequenced real KRAS amplicons, with variants spiked in at specific ratios, to assess which caller performs best in terms of both variant detection and assignment of allelic frequencies. We also assessed the sequencing depths required to detect low‐allelic fraction variants. We found that VarScan2 performed best overall with sequencing depths of 100×, 250×, 500×, and 1,000× required to accurately identify variants present at 10%, 5%, 2.5%, and 1%, respectively.  相似文献   
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GM2 gangliosidosis is a fatal lysosomal storage disease caused by a deficiency of β-hexosaminidase (EC 3.2.1.52). There are two major isoforms of the enzyme: hexosaminidase A composed of an α and a β subunit (encoded by HEXA and HEXB genes, respectively); and, hexosaminidase B composed of two β subunits. Hexosaminidase A requires an activator protein encoded by GM2A to catabolize GM2 ganglioside, but even in the absence of the activator protein, it can hydrolyze the synthetic substrates commonly used to assess enzyme activity. GM2 gangliosidosis has been reported in Japanese Chin dogs, and we identified the disease in two related Japanese Chin dogs based on clinical signs, histopathology and elevated brain GM2 gangliosides. As in previous reports, we found normal or elevated hexosaminidase activity when measured with the synthetic substrates. This suggested that the canine disease is analogous to human AB variant of GM2 gangliosidosis, which results from mutations in GM2A. However, only common neutral single nucleotide polymorphisms were found upon sequence analysis of the canine ortholog of GM2A from the affected Japanese Chins. When the same DNA samples were used to sequence HEXA, we identified a homozygous HEXA:c967G>A transition which predicts a p.E323K substitution. The glutamyl moiety at 323 is known to make an essential contribution to the active site of hexosaminidase A, and none of the 128 normal Japanese Chins and 92 normal dogs of other breeds that we tested was homozygous for HEXA:c967A. Thus it appears that the HEXA:c967G>A transition is responsible for the GM2 gangliosidosis in Japanese Chins.  相似文献   
100.

Background

Despite the huge burden of HIV in sub-Saharan Africa, there is little evidence of the multidimensional needs of patients with HIV infection to inform the person-centred care across physical, psychological, social and spiritual domains stipulated in policy guidance. We aimed to describe the problems experienced by people with HIV in Kenya and Uganda and the management of these problems by HIV outpatient services.

Methods

Local researchers conducted in depth qualitative interviews with HIV patients, caregivers and service staff at 12 HIV outpatient facilities (6 in Kenya, 6 in Uganda). Interview data were analysed thematically.

Results

189 people were interviewed (83 patients, 47 caregivers, 59 staff). The impact of pain and symptoms and their causes (HIV, comorbidities, treatment side-effects) were described. Staff reported that effective pain relief was not always available, particularly in Kenya. Psychosocial distress (isolation, loneliness, worry) was exacerbated by stigma and poverty, and detrimentally affected adherence. Illness led to despair and hopelessness. Provision of counselling was reported, but spiritual support appeared to be less common. Neither pain nor psychosocial problems were routinely reported to service staff. Collaboration with local hospices and income-generation activities for patients were highlighted as useful.

Conclusions

The findings demonstrate the multiple and interrelated problems associated with living with HIV and how psychosocial and spiritual distress can contribute to 'total pain’ in this population. In line with the palliative care approach, HIV care requires holistic care and assessment that take into account psychological, socioeconomic and spiritual distress alongside improved access to pain-relieving drugs, including opioids.
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