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991.
Zebrack BJ Eshelman DA Hudson MM Mertens AC Cotter KL Foster BM Loftis L Sozio M Oeffinger KC 《Cancer》2004,100(4):843-850
BACKGROUND: Most children diagnosed with cancer are surviving into adulthood but are not receiving adequate or appropriate follow-up health care. However, to the authors' knowledge, there is little literature published to date exploring potential barriers to long-term risk-based follow-up care for young adult survivors of childhood cancer. METHODS: In the current study, using a modified Delphi technique, young adult cancer survivors identified barriers to utilizing appropriate follow-up care and offered suggestions for ways to enhance health care in this young adult population. RESULTS: Major barriers to health care were found to be a lack of knowledge on the part of both physicians and survivors regarding long-term health issues related to cancer. Suggestions to enhance care included self-advocacy training for survivors and advanced training for primary care physicians who may treat childhood cancer survivors as they transition into adulthood. CONCLUSIONS: The results of the current study are consistent with reports that young adult survivors of childhood cancer need or desire information regarding their medical histories, psychosocial support, and social advocacy. 相似文献
992.
Buchholz TA Weil MM Ashorn CL Strom EA Sigurdson A Bondy M Chakraborty R Cox JD McNeese MD Story MD 《Cancer》2004,100(7):1345-1351
BACKGROUND: Mothers of children who have ataxia telangiectasia have been reported to be at increased risk for development of breast carcinoma. To test whether sequence variants in the ataxia telangiectasia, mutated, gene (ATM) are associated with breast carcinoma, the authors compared the frequency of ATM cDNA sequence changes in patients with breast carcinoma with the corresponding frequency in control patients. METHODS: The authors sequenced ATM cDNA from 91 patients with breast carcinoma and compared the frequencies of sequence changes in these patients with the corresponding frequencies in a control sample of 940 individuals with no history of malignant disease. RESULTS: Thirty-five patients with breast carcinoma had one or more single-base changes in ATM. Three genetic variants were found in at least two patients. These variants resulted in Asp1853Asn, Pro1054Arg, or Ser49Cys amino acid substitutions in the ATM protein. The Ser49Cys variant was more common in patients with breast carcinoma than in the control patients, with respective frequencies of 6.7% (5 of 75 patients) and 1.3% (12 of 940 patients; P=0.006; Fisher two-sided exact test). The subgroup of patients with bilateral breast carcinoma had a Ser49Cys frequency of 11.8% (2 of 17 patients), which again was significantly different from what was observed in the control group (P=0.024; Fisher two-sided exact test). The allele frequencies of the other two variants were not different between case patients and control patients. CONCLUSIONS: Patients with breast carcinoma, particularly those with bilateral disease, were more likely to have a variant in the ATM gene that resulted in a Ser49Cys substitution in the gene product. Additional studies are needed to evaluate the potential functional consequences of the Ser49Cys substitution and confirm the relevance of this variant in the development of breast carcinoma. 相似文献
993.
The primary tumors that typically cause carcinomatous meningitis include lung cancer, breast cancer, leukemia, lymphoma and melanoma. A variety of neurological signs and symptoms can be seen depending on the extent and location of the meningeal metastasis. Once the diagnosis of carcinomatous meningitis is confirmed, the search for the primary tumor can be a challenge and at times may require extensive radiographic or even surgical evaluation to obtain specimen for pathological confirmation. Here we report a patient who presented with bilateral cranial nerve VIII and cerebellar symptoms, and was diagnosed with carcinomatous meningitis. Only after an exploratory laporatomy did it become clear that the initial symptoms were related to a metastatic gallbladder carcinoma. 相似文献
994.
Acute radiation dermatitis commonly occurs following local radiation therapy for various cancers and, when severe, may necessitate disruption of treatment. Intense inflammatory reaction may result in a breakdown of the skin's barrier function and accompanying bacterial colonization. Bacterial superantigens may exacerbate inflammation through activation of T-cells and subsequent cytokine release. We report six cases of severe radiation dermatitis in cancer patients. Four of the six grew pathogenic bacteria, and three had psoriasiform or eczematous reactions at distant sites. Both the radiation dermatitis and the distant cutaneous reactions resolved rapidly on a combination of topical steroids and oral plus topical antibiotic therapy. We suggest that staphylococcal superinfection of acute radiodermatitis intensifies the inflammatory process and hinders repair of the epidermal barrier. Patients with acute radiation dermatitis should be investigated for secondary infection. We emphasize the importance of including topical and oral antibiotic therapy in conjunction with topical corticosteroids to eradicate infection as well as hasten repair of the skin's barrier function. These cases are presented to call attention to the role of Staphylococcus aureus in the pathogenesis of severe radiation dermatitis and the need to include appropriate antibiotic therapy based on culture in the management of acute radiation dermatitis. 相似文献
995.
Gelmini S Poggesi M Distante V Bianchi S Simi L Luconi M Raggi CC Cataliotti L Pazzagli M Orlando C 《Cancer letters》2004,216(1):81-87
Tankyrase promotes telomere elongation by interaction with the telomeric protein binding factor TRF1, a negative regulator of telomere extension. We measured tankyrase mRNA by real-time RT-PCR in 66 breast cancers and in paired normal tissues. Results were compared with hTERT mRNA expression. The levels of tankyrase in breast cancers were significantly higher in comparison to normal tissues (P<0.0001) and significantly related to the status of progesterone receptors. No relationship was found between tankyrase and hTERT mRNA expression in breast cancers. According to our results, tankyrase expression appeared up regulated in breast cancers. 相似文献
996.
Rosenthal E McCrory A Talbert M Young G Murphy-Ullrich J Gladson C 《Molecular carcinogenesis》2004,40(2):116-121
Head and neck cancers are characterized by a vigorous desmoplastic response, but the contribution of stromal-derived growth factors to the tumor microenvironment is poorly understood. We evaluated the expression of stromal growth factor expression in head and neck squamous cell carcinoma (HNSCC) in normal and tumor-associated stromal cells. Stromal tissue was isolated from epithelial cells with laser capture microdissection (LCMD) and analyzed by cDNA array for the expression of TGFalpha, TGF-beta1, HGF, PDGF-alpha, IGFII, bFGF, aFGF, VEGFC, and VEGF. Primary fibroblasts were isolated in vitro from HNSCC tumors, adjacent histologically normal mucosa, and skin in vitro. Fibroblast populations were assessed for TGF-beta1 expression by ELISA and luciferase reporter assay to assess protein expression. We identified TGF-beta1 and IGFII overexpression in normal and tumor-associated stromal cells; however, only TGF-beta1 was significantly overexpressed (3.4-fold) in tumor-associated stroma. Assessment of carcinoma-associated fibroblasts (CAFs), normal dermal fibroblasts (NDFs), and normal mucosal fibroblasts (NMFs) in propagated fibroblasts demonstrated persistently elevated levels of TGF-beta1 in CAFs compared to NMF and NDF populations. Elevated levels of TGF-beta1 were identified in the stromal compartment of HNSCC tumors compared to normal mucosa by immunohistochemical analysis. These results suggest that TGF-beta1 mRNA and protein is specifically upregulated in CAFs in vitro and in vivo. 相似文献
997.
Rad51 overexpression promotes alternative double-strand break repair pathways and genome instability 总被引:12,自引:0,他引:12
Genomic instability is characteristic of tumor cells, and a strong correlation exists between abnormal karyotype and tumorigenicity. Increased expression of the homologous recombination and DNA repair protein Rad51 has been reported in immortalized and tumor cells, which could alter recombination pathways to contribute to the chromosomal rearrangements found in these cells. We used a genetic system to examine the potential for multiple double-strand breaks to lead to genome rearrangements in the presence of increased Rad51 expression. Analysis of repair revealed a novel class of products consistent with crossing over, involving gene conversion associated with an exchange of flanking markers leading to chromosomal translocations. Increased Rad51 also promoted aneuploidy and multiple chromosomal rearrangements. These data provide a link between elevated Rad51 protein levels, genome instability, and tumor progression. 相似文献
998.
Brca1 inactivation induces p27(Kip1)-dependent cell cycle arrest and delayed development in the mouse mammary gland 总被引:1,自引:0,他引:1
One common characteristic of breast cancers arising in carriers of the predisposition gene BRCA1 is a loss of expression of the CDK inhibitor p27(Kip1) (p27), suggesting that p27 interacts epistatically with BRCA1. To investigate this relationship, we examined expression of p27 in mice expressing a dominant negative allele of Brca1 (MMTV-trBr) in the mammary gland. While these mice rarely develop tumors, they showed a 50% increase in p27 protein and a delay in mammary gland development associated with reduced proliferation. In contrast, on a p27 heterozygote background, MMTV-trBrca1 mice showed an increase in S phase cells, and normal mammary development. p27 was the only protein in the cyclin-cyclin-dependent kinase network to show altered expression, suggesting that it may be a central mediator of cell cycle arrest in response to loss of function of BRCA1. Furthermore, in human mammary epithelial MCF7 cells expressing BRCA1-specific RNAi and in the BRCA1-deficient human tumor cell line HCC1937, p27 is elevated at the mRNA level compared to cells expressing wild-type BRCA1. We hypothesize that disruption of BRCA1 induces an increase in p27 that inhibits proliferation. Accordingly, reduction in p27 expression leads to enhancement of cellular proliferation in the absence of BRCA1. 相似文献
999.
Relation of metformin treatment to clinical events in diabetic patients undergoing percutaneous intervention 总被引:1,自引:0,他引:1
Kao J Tobis J McClelland RL Heaton MR Davis BR Holmes DR Currier JW;Investigators in the Prevention of Restenosis With Tranilast Its Outcomes Trial 《The American journal of cardiology》2004,93(11):1347-50, A5
Diabetic patients undergoing coronary interventions have worse clinical and angiographic outcomes than do patients without diabetes. Metformin, an insulin sensitizer, may decrease the occurrence of these outcomes. Diabetic patients in the Prevention of Restenosis with Tranilast and its Outcomes Trial were identified through their medical records (n = 2,772). In this trial, 1,110 diabetic patients received nonsensitizer therapy (insulin and/or sulfonylureas) and 887 received sensitizer therapy (metformin with or without additional therapy). Logistic regression was used to obtain odds ratios (ORs) (sensitizer vs nonsensitizer therapy) of any clinical event (death, myocardial infarction, or ischemia-driven target vessel revascularization) and adjusted for multiple risk factors. Multivariate analysis showed no effect of lesion characteristics on clinical outcomes. Compared with patients on nonsensitizer therapy, those on sensitizer therapy showed an adjusted OR of 0.72 (95% confidence interval [CI] 0.57 to 0.91, p = 0.005) for any clinical event. The differences between the nonsensitizer therapy group and the sensitizer group were attributable mainly to decreased rates of death (OR 0.39, 95% CI 0.19 to 0.77, p = 0.007) and myocardial infarction (OR 0.31, 95% CI 0.15 to 0.66, p = 0.002). In our retrospective analysis, use of metformin in diabetics undergoing coronary interventions appeared to decrease adverse clinical events, especially death and myocardial infarction, compared with diabetic patients treated with nonsensitizer therapy. 相似文献
1000.