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51.
Kosuke Yoshihara Takayuki Enomoto Daisuke Aoki Yoh Watanabe Junzo Kigawa Nobuhiro Takeshima Hyoe Inomata Kana Hattori Masahisa Jinushi Hitoshi Tsuda Toru Sugiyama 《Cancer science》2020,111(9):3350-3358
Whether germline (g) breast cancer susceptibility gene (BRCA) mutations are located within or outside the ovarian cancer cluster region (OCCR) (1380‐4062 bp for gBRCA1, and between 3249‐5681 bp and 6645‐7471 bp for gBRCA2) may influence risk variations for ovarian cancers. This ad hoc analysis of the CHARLOTTE epidemiological study in Japan assessed the distribution of gBRCA1/2 mutations in patients with newly diagnosed ovarian cancer, and investigated an association between gBRCA1/2 mutation locations and ovarian cancer risk. Differences in patient background and clinical characteristics in subgroups stratified by gBRCA1/2 mutation locations were also evaluated. We analyzed the data of 93 patients (14.7%) from the CHARLOTTE study who were positive for gBRCA1/2 mutations. After excluding 16 cases with L63X founder mutation, 28 (65.1%) of gBRCA1 mutations were within the OCCR. Of 30 gBRCA2 mutations, 15 (50.0%) were within the OCCR. Of 27 patients (one patient excluded for unknown family history) with gBRCA1 mutations located in the OCCR, 11 (40.7%) had a family history of ovarian cancer; the proportion of patients with a family history of ovarian cancer and gBRCA1 mutations outside the OCCR was lower (13.3%). Sixty percent of patients with gBRCA1 mutations outside the OCCR had a family history of breast cancer; the proportion of patients with a family history of breast cancer and gBRCA1 mutations within the OCCR was relatively lower (33.3%). Understanding the mutation locations may contribute to more accurate risk assessments of susceptible individuals and early detection of ovarian cancer among gBRCA mutation carriers. 相似文献
52.
Fuying Chen Linting Huang Changcan Li Jia Zhang Weiqin Yang Beibei Zhang Huaguo Li Dan Deng Jianying Liang Jinwen Shen Zhirong Yao Ming Li 《Clinical genetics》2020,98(2):179-184
Epidermolysis bullosa (EB) is a heritable blistering disorder. We performed a next-generation sequencing-based multigene panel test and successfully predicted 100% of the EB types, including, 36 EB simplex (EBS), 13 junctional EB (JEB), 86 dystrophic EB (DEB), and 3 Kindler EB. Chinese JEB and recessive DEB (RDEB) patients have relatively mild phenotypes; for severe type separately accounts for 45.5% and 23.8%, respectively. We identified 96 novel and 49 recurrent pathogenic variants in 11 genes, although we failed to detect the second mutation in one JEB and five RDEB patients. We identified one novel p.E475K mosaic mutation in the clinically normal mother of one out of 13 EBS patients with KRT5 mutations, one recurrent p.G2034R mosaic mutation, and one novel p.G2043R mosaic mutation in the clinically normal relatives of two out of 19 dominant DEB patients. This study shows that next-generation technology could be an effective tool in diagnosing EB. 相似文献
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ABSTRACTAlthough exclusive breastfeeding has been linked to lower rates of postnatal HIV transmission compared to nonexclusive breastfeeding, mechanisms underlying this are unclear. Across a longitudinally sampled cohort of South African infants, we showed that exclusively breastfed (EBF) infants had altered gut bacterial communities when compared to nonexclusively breastfed (NEBF) infants, as well as reduced peripheral CD4 + T cell activation and lowered chemokine and chemokine receptor expression in the oral mucosa. We further demonstrated that the relative abundance of key taxa was correlated with peripheral CD4 + T cell activation. Here, we supplement those findings by using compositional data analyses to identify shifts in the abundance of several Bifidobacteria strains relative to select strains of Escherichia, Bacteroides, and others that are associated with the transition to NEBF. We illustrate that the abundance ratio of these taxa is tightly correlated with feeding modality and is a strong predictor of peripheral T cell activation. More broadly, we discuss our study in the context of novel developments and explore future directions for the field. 相似文献
57.
Rosa Della Monica Mariella Cuomo Roberta Visconti Annabella di Mauro Michela Buonaiuto Davide Costabile Giulia De Riso Teodolinda Di Risi Elia Guadagno Roberto Tafuto Sabrina Lamia Alessandro Ottaiano Paolo Cappabianca Maria Laura Del Basso de Caro Fabiana Tatangelo Juergen Hench Stephan Frank Salvatore Tafuto Lorenzo Chiariotti 《Oncology research》2020,28(9):837-845
Unresectable neuroendocrine neoplasms (NENs) often poorly respond to standard therapeutic approaches.
Alkylating agents, in particular temozolomide, commonly used to treat high-grade brain tumors including glioblastomas, have recently been tested in advanced or metastatic NENs, where they showed promising response
rates. In glioblastomas, prediction of response to temozolomide is based on the assessment of the methylation
status of the MGMT gene, as its product, O6
-methylguanine-DNA methyltransferase, may counteract the damaging effects of the alkylating agent. However, in NENs, such a biomarker has not been validated yet. Thus, we
have investigated MGMT methylation in 42 NENs of different grades and from various sites of origin by two
different approaches: in contrast to methylation-specific PCR (MSP), which is commonly used in glioblastoma
management, amplicon bisulfite sequencing (ABS) is based on high-resolution, next-generation sequencing
and interrogates several additional CpG sites compared to those covered by MSP. Overall, we found MGMT
methylation in 74% (31/42) of the NENs investigated. A higher methylation degree was observed in welldifferentiated tumors and in tumors originating in the gastrointestinal tract. Comparing MSP and ABS results,
we demonstrate that the region analyzed by the MSP test is sufficiently informative of the MGMT methylation
status in NENs, suggesting that this predictive parameter could routinely be interrogated also in NENs. 相似文献
58.
乳腺癌是一类具有异质性的肿瘤,不同患者的治疗方法和疗效都不相同。尽管目前仍在努力为激素受体(hormone receptor,HR)阳性(+)、人表皮生长因子受体2(human epidermal growth factor receptor 2,HER-2)阴性(-)、淋巴结(axillary lymph node,ALN)阴性(-)的早期乳腺癌患者寻找合适的治疗方法,但其术后是否需要化疗仍然是肿瘤科医生面临的一个难题。以往治疗主要依赖于经典的组织病理学和免疫组织化学技术,随着精准医疗时代的到来,我们需要更定量的诊断方法和合理的个体化治疗。虽然化疗可降低疾病复发风险并提高生存率,但它带来的不良反应事件会降低患者的生活质量,尤其低复发风险(recurrence risk,RS)有可能超过化疗益处。21基因检测不仅可以预测这类早期乳腺癌化疗疗效及评估预后,还可提供精准的个体化治疗方案指导用药,为患者增添信心。本文就乳腺癌21基因检测的研究进展进行综述。 相似文献
59.
Yoshinori Yanai Takeo Kosaka Kohei Nakamura Eriko Aimono Kazuhiro Matsumoto Shinya Morita Shuji Mikami Hiroshi Nishihara Mototsugu Oya 《Cancer science》2020,111(12):4652
Cyclin‐dependent kinase 12 (CDK12), one of the key factors associated with DNA damage response pathways, is located on chromosome 17 proximal to Erb‐B2 receptor tyrosine kinase 2 (ERBB2). In this report, CDK12 and ERBB2 coamplification was detected by targeted next‐generation sequencing in two urothelial carcinomas. The staining intensity of the CDK12 and human epidermal growth factor receptor‐2 proteins was associated with the prognosis of each urothelial carcinoma case. Our results suggest that CDK12 coamplification with ERBB2 might be associated with tumor aggressiveness and contribution to cancer pathogenesis. Therapies targeting CDK12 should be developed for these patients. 相似文献
60.
《Vaccine》2020,38(39):6141-6152
Influenza vaccination is considered the most valuable means to prevent and control seasonal influenza infections, which causes various clinical symptoms, ranging from mild cough and fever to even death. Among various influenza vaccine types, the inactivated subunit type is known to provide improved safety with reduced reactogenicity. However, there are some drawbacks associated with inactivated subunit type vaccines, with the main ones being its low immunogenicity and the induction of Th2-biased immune responses. In this study, we investigated the role of a single-stranded RNA (ssRNA) derived from the intergenic region in the internal ribosome entry site of the Cricket paralysis virus as an adjuvant rather than the universal vaccine for a seasonal inactivated subunit influenza vaccine. The ssRNA adjuvant stimulated not only well-balanced cellular (indicated by IgG2a, IFN-γ, IL-2, and TNF-α) and humoral (indicated by IgG1 and IL-4) immune responses but also a mucosal immune response (indicated by IgA), a key protector against respiratory virus infections. It also increases the HI titer, the surrogate marker of influenza vaccine efficacy. Furthermore, ssRNA adjuvant confers cross-protective immune responses against heterologous influenza virus infection while promoting enhanced viral clearance. Moreover, ssRNA adjuvant increases the number of memory CD4+ and CD8+ T cells, which can be expected to induce long-term immune responses. Therefore, this ssRNA-adjuvanted seasonal inactivated subunit influenza vaccine might be the best influenza vaccine generating robust humoral and cellular immune responses and conferring cross-protective and long-term immunity. 相似文献