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841.
842.
《Chronobiology international》2013,30(5):668-679
Systemic low doses of the endotoxin lipopolysaccharide (LPS, 100?µg/kg) administered during the early night induce phase-delays of locomotor activity rhythms in mice. Our aim was to evaluate the role of tumor necrosis factor (Tnf)-alpha and its receptor 1/p55 (Tnfr1) in the modulation of LPS-induced circadian effects on the suprachiasmatic nucleus (SCN). We observed that Tnfr1-defective mice (Tnfr1 KO), although exhibiting similar circadian behavior and light response to that of control mice, did not show LPS-induced phase-delays of locomotor activity rhythms, nor LPS-induced cFos and Per2 expression in the SCN and Per1 expression in the paraventricular hypothalamic nucleus (PVN) as compared to wild-type (WT) mice. We also analyzed Tnfr1 expression in the SCN of WT mice, peaking during the early night, when LPS has a circadian effect. Peripheral inoculation of LPS induced an increase in cytokine/chemokine levels (Tnf, Il-6 and Ccl2) in the SCN and in the PVN. In conclusion, in this study, we show that LPS-induced circadian responses are mediated by Tnf. Our results also suggest that this cytokine stimulates the SCN after LPS peripheral inoculation; and the time-related effect of LPS (i.e. phase shifts elicited only at early night) might depend on the increased levels of Tnfr1 expression. We also confirmed that LPS modulates clock gene expression in the SCN and PVN in WT but not in Tnfr1 KO mice.Highlights: We demonstrate a fundamental role for Tnf and its receptor in circadian modulation by immune stimuli at the level of the SCN biological clock. 相似文献
843.
Pospichalova V Tureckova J Fafilek B Vojtechova M Krausova M Lukas J Sloncova E Takacova S Divoky V Leprince D Plachy J Korinek V 《Genesis (New York, N.Y. : 2000)》2011,49(3):142-151
HIC1 (hypermethylated in cancer 1) is a tumor suppressor gene located on chromosome 17p13.3, a region frequently hypermethylated or deleted in human neoplasias. In mouse, Hic1 is essential for embryonic development and exerts an antitumor role in adult animals. Since Hic1-deficient mice die perinatally, we generated a conditional Hic1 null allele by flanking the Hic1-coding region by loxP sites. When crossed to animals expressing Cre recombinase in a cell-specific manner, the Hic1 conditional mice will provide new insights into the function of Hic1 in developing and mature tissues. Additionally, we used gene targeting to replace sequence-encoding amino acids 186-893 of Hic1 by citrine fluorescent protein cDNA. We demonstrate that the distribution of Hic1-citrine fusion polypeptide corresponds to the expression pattern of wild-type Hic1. Consequently, Hic1-citrine "reporter" mice can be used to monitor the activity of the Hic1 locus using citrine fluorescence. 相似文献
844.
845.
Summary Two stable epithelial-like cell lines, the pig kidney strain (LLC-PK1) and a Wilms' tumor line (TuWi), previously established in other laboratories, were found to exhibit a number of properties
characteristic of kidney proximal tubular epithelium. Electron micrographs of LLC-PK1 monolayers revealed cells forming rosettes reminiscent of tubules. Numerous elongated microvilli and an amorphous basal laminar
material surrounded the cell membranes. Cell junctions were located between cell membranes at regions adjacent to the patent
lumens. Wilms' cells in culture were similar in appearance to the pig kidney cells; they exhibited numerous microvilli, a
thin basal laminar coating on the membrane, and desmonsomes between cells. No rosette formation was evident. Neither cell
line was found to produce extracellular reticulin fibers when grown in the presence ofl-ascorbic acid for 1 week. Absence of stainable reticulin in cell monolayer culture after ascorbicacid treatment has been
noted only in cell lines of apparent epithelial origin. Histochemically, both lines reacted positively for activities of a
number of enzymes found in high amounts in normal kidney tubular epithelium. Pig kidney cells were highly positive for γ-glutamyl
transpeptidase activity and moderately active for acid phosphatase and leucine aminopeptidase activities. Wilms' tumor cells
were markedly active for γ-glutamyl transpeptidase, 5′-nucleotidase, ATPase, glucose-6-phosphatase, and acid phosphatase activities.
These findings in conjunction with the ultrastructural observations indicate that these two lines in culture maintain many
of the properties typical of proximal kidney tubular epithelium. 相似文献
846.
Patricia M. LoRusso Kurt Schalper Jeffrey Sosman 《Pigment cell & melanoma research》2020,33(3):390-402
Targeted therapy directed against oncogenic BRAF mutations and immune checkpoint inhibitors have transformed melanoma therapy over the past decade and prominently improved patient outcomes. However, not all patients will respond to targeted therapy or immunotherapy and many relapse after initially responding to treatment. This unmet need presents two major challenges. First, can we elucidate novel oncogenic drivers to provide new therapeutic targets? Second, can we identify patients who are most likely to respond to current therapeutic strategies in order to both more accurately select populations and avoid undue drug exposure in patients unlikely to respond? In an effort to evaluate the current state of the field with respect to these questions, we provide an overview of some common oncogenic mutations in patients with metastatic melanoma and ongoing efforts to therapeutically target these populations, as well as a discussion of biomarkers for response to immune checkpoint inhibitors—including tumor programmed death ligand 1 expression and the future use of neoantigens as a means of truly personalized therapy. This information is becoming important in treatment decision making and provides the framework for a treatment algorithm based on the current landscape in metastatic melanoma. 相似文献
847.
Shimeng Li Baoxiang Pan Lihong Li Bo Shi Feng Xie Chengyan He 《Journal of cellular physiology》2019,234(10):18111-18122
X-linked inhibitor of apoptosis protein (XIAP) is aberrantly expressed in solid tumors. Considering conflicting data, we conducted this meta-analysis to investigate its prognostic role. Electronic databases were searched to collect studies about associations between XIAP expressions and survival outcomes. Hazard ratio (HR), odds ratio (OR), and 95% confidence interval (CI) were utilized as effect size estimates. A total of 3,794 patients from 21 published studies were included. The results revealed that high XIAP expressions correlated with age (OR = 2.02; 95% CI, 1.07–3.84), lymph node metastasis (OR = 1.69; 95% CI, 1.02–2.77), histological grade (OR = 2.04; 95% CI, 1.01–4.11), and tumor stage (OR = 2.18; 95% CI, 1.20–3.96). The combined HR revealed that high XIAP expressions associated with poor overall survival (OS) (HR = 1.60; 95% CI, 1.22–2.10). Our study suggested high XIAP expressions may be indicative of poor prognosis in solid tumors. 相似文献
848.
The E3 ligase HERC4 is overexpressed in human breast cancer and its expression levels correlated with the prognosis of breast cancer patients. However, the roles of HERC4 in mammary tumorigenesis remain unclear. Here we demonstrate that the knockdown of HERC4 in human breast cancer cells dramatically suppressed their proliferation, survival, migration, and tumor growth in vivo, while the overexpression of HERC4 promoted their aggressive tumorigenic activities. HERC4 is a new E3 ligase for the tumor suppressor LATS1 and destabilizes LATS1 by promoting the ubiquitination of LATS1. miRNA-136-5p and miRNA-1285-5p, expression of which is decreased in human breast cancers and is inversely correlated with the prognosis of breast cancer patients, are directly involved in suppressing the expression of HERC4. In summary, we discover a miRNA-HERC4-LATS1 pathway that plays important roles in the pathogenesis of breast cancer and represents new therapeutic targets for human breast cancer. 相似文献
849.
应用RT-PCR、Westem blot、免疫组化分别检测甲状腺乳头状癌组织与癌旁正常甲状腺组织标本中DcR3mRNA及蛋白的表达情况,探讨DcR3在甲状腺乳头状癌组织中的表达及,临床意义。RT-PCR检测显示,甲状腺乳头状癌中DcR3 mRNA的表达明显高于正常甲状腺组织(P〈0.05):Western blot提示,DcR3蛋白在甲状腺乳头状癌中表达比正常甲状腺组织高(P〈0.05);免疫组化显示,DcR3蛋白在甲状腺乳头状癌中高表达(P〈0.05)。DcR3mRNA及蛋白质在甲状腺乳头状癌及正常甲状腺组织间的表达差异有统计学意义(P〈0.05)。DcR3基因及蛋白在甲状腺乳头状癌中高表达,提示DcR3可能促进了甲状腺乳头状癌的发生发展。 相似文献
850.
Susana Solá Ana L. Morgado Cecília M.P. Rodrigues 《Biochimica et Biophysica Acta (BBA)/General Subjects》2013