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991.
Borrelia burgdorferi sensu lato is the causative agent of Lyme disease, which afflicts both humans and some domestic animals. B. burgdorferi, a highly evolved extracellular pathogen, uses several strategies to survive in a complex enzootic cycle involving a diverse range of hosts. This review focuses on the unique adaptive features of B. burgdorferi, which are central to establishing a successful spirochetal infection within arthropod and vertebrate hosts. We also discuss the regulatory mechanisms linked with the development of molecular adaptation of spirochetes within different host environments. 相似文献
992.
CARF is a novel protein that cooperates with mouse p19ARF (human p14ARF) in activating p53 总被引:2,自引:0,他引:2
Hasan MK Yaguchi T Sugihara T Kumar PK Taira K Reddel RR Kaul SC Wadhwa R 《The Journal of biological chemistry》2002,277(40):37765-37770
The INK4a locus on chromosome 9p21 encodes two structurally distinct tumor suppressor proteins, p16(INK4a) and the alternative reading frame protein, ARF (p19(ARF) in mouse and p14(ARF) in human). Each of these proteins has a role in senescence of primary cells and activates pathways for cell cycle control and tumor suppression. The current prevailing model proposes that p19(ARF) activates p53 function by antagonizing its degradation by MDM2. It was, however, recently shown that stabilization of p53 by p14(ARF) occurs independent of the relocalization of MDM2 to the nucleolus. We have identified a novel collaborator of ARF, CARF. It co-localizes and interacts with ARF in the nucleolus. We demonstrate that CARF is co-regulated with ARF, cooperates with it in activating p53, and thus acts as a novel component of the ARF-p53-p21 pathway. 相似文献
993.
994.
Sahu NP Pal C Mandal NB Banerjee S Raha M Kundu AP Basu A Ghosh M Roy K Bandyopadhyay S 《Bioorganic & medicinal chemistry》2002,10(6):1687-1693
Some novel quinoline derivatives were prepared and tested for antileishmanial activity. 2-(2-Methylquinolin-4-ylamino)-N-phenylacetamide (2) was found to be significantly more active than the standard antileishmanial drug sodium antimony gluconate (SAG) in reducing the parasite load both in the spleen and liver at a much lower concentration in hamster models. The results suggest that the compound could be exploited as an antileishmanial drug. 相似文献
995.
Madhavan GR Chakrabarti R Vikramadithyan RK Mamidi RN Balraju V Rajesh BM Misra P Kumar SK Lohray BB Lohray VB Rajagopalan R 《Bioorganic & medicinal chemistry》2002,10(8):2671-2680
A series of pyrimidinone derivatives of thiazolidinediones were synthesized. Their biological activity were evaluated in insulin resistant, hyperglycemic and obese db/db mice. In vitro PPARgamma transactivation assay was performed in HEK 293T cells. PMT13 showed the best biological activity in this series. PMT13 (5-[4-[2-[2-ethyl-4-methyl-6-oxo-1,6-dihydro-1-pyrimidinyl]ethoxy]phenylmethyl]thiazolidine-2,4-dione) showed better plasma glucose, triglyceride and insulin-lowering activity in db/db mice than rosiglitazone and pioglitazone. PMT13 showed better PPARgamma transactivation than the standard compounds. Pharmacokinetic study in Wistar rats showed good systemic exposure of PMT13. Twenty-eight day oral toxicity study in Wistar rats did not show any treatment-related adverse effects. 相似文献
996.
Sunil VR Connor AJ Guo Y Laskin JD Laskin DL 《American journal of physiology. Lung cellular and molecular physiology》2002,282(4):L872-L880
Lung injury induced by acute endotoxemia is associated with increased generation of inflammatory mediators such as nitric oxide and eicosanoids, which have been implicated in the pathophysiological process. Although production of these mediators by alveolar macrophages (AM) has been characterized, the response of type II cells is unknown and was assessed in the present studies. Acute endotoxemia caused a rapid (within 1 h) and prolonged (up to 48 h) induction of nitric oxide synthase-2 (NOS-2) in type II cells but a delayed response in AM (12-24 h). In both cell types, this was associated with increased nitric oxide production. Although type II cells, and to a lesser extent AM, constitutively expressed cyclooxygenase-2, acute endotoxemia did not alter this activity. Endotoxin administration had no effect on mitogen-activated protein kinase or protein kinase B-alpha (PKB-alpha) expression. However, increases in phosphoinositide 3-kinase and phospho-PKB-alpha were observed in type II cells. The finding that this was delayed for 12-24 h suggests that these proteins do not play a significant role in the regulation of NOS-2 in this model. After endotoxin administration to rats, a rapid (within 1-2 h) activation of nuclear factor-kappaB was observed. This response was transient in type II cells but was sustained in AM. Interferon regulatory factor-1 (IRF-1) was also activated rapidly in type II cells. In contrast, IRF-1 activation was delayed in AM. These data demonstrate that type II cells, like AM, are highly responsive during acute endotoxemia and may contribute to pulmonary inflammation. 相似文献
997.
Harsh?Pal?Bais Travis?S.?Walker Janeen?J.?McGrew Jorge?M.?VivancoEmail author 《In vitro cellular & developmental biology. Plant》2002,38(1):58-65
Summary Use of Hypericum perforatum L., commonly known as St. John's wort, has increased recently due to the pharmaceutical potential
of hypericin, found in its leaves. Hypericin has been reported to effect a natural treatment for mild and moderate depression
by increasing the concentration of neurotransmitters in the central nervous system. We have developed a novel cell culture
system for in vitro growth and production of this species, suggesting a possible technology for large-scale production of
hypericin. Leaf explants grown in Murashige and Skoog salts supplemented with 2,4-dichlorophenoxyacetic acid (0.90 μM) and
kinetin (0.11 μM) gave maximum percentage callus formation compared to other medium treatments evaluated. Hypericin localization
in cell phase and leaves was found to vary, with cell phase accumulating hypericin in special organelles and leaves accumulating
it in vacuoles. Light and dark conditions, with cell aggregate size, played important roles in growth and hypericin production
in cell suspension cultures. 相似文献
998.
Adenoviral transfer of mda-7 leads to BAX up-regulation and apoptosis in mesothelioma cells,and is abrogated by over-expression of BCL-XL 总被引:8,自引:0,他引:8
999.
Schafer JM Bentrem DJ Takei H Gajdos C Badve S Jordan VC 《The Journal of steroid biochemistry and molecular biology》2002,83(1-5):75-83
Drug resistance to tamoxifen (Tam) is a significant clinical problem but the mechanism through which this occurs remains elusive. We have developed a number of xenograft models of Tam-stimulated growth that model breast cancer progression using estrogen receptor positive MCF-7 or T47D breast cancer cells. When estrogen-stimulated T47D:E2 tumors are treated long term with Tam, Tam-stimulated tumors develop (T47D:Tam) that are stimulated by both estrogen and Tam. When HER-2/neu status is determined, it is clear that the T47D:Tam tumors express significantly higher levels of HER-2/neu protein by immunohistochemistry and mRNA as measured by real-time RT-PCR. The T47D:Tam tumors also express higher levels of estrogen receptor and progesterone receptor protein than their estrogen-stimulated T47D:E2 counterparts. We compared out results to the MCF-7 model of Tam-stimulated growth. The MCF-7:Tam ST (estrogen- and Tam-stimulated) and MCF-7:Tam LT (estrogen-inhibited, Tam-stimulated) were bilaterally transplanted to account for any mouse to mouse variation and characteristic growth patterns were observed. TUNEL staining was performed on MCF-7:Tam LT treated with either estrogen or Tam and it was concluded that estrogen-inhibited tumor growth was a result of increased apoptosis. Three phases of tumor progression are described that involve increases in HER-2/neu expression, de-regulation of estrogen receptor expression and increases in apoptosis which in concert determine the phenotype of drug resistance to Tam. 相似文献
1000.
The Arabidopsis thaliana genome has two genes (AtFC-I and AtFC-II), encoding ferrochelatase, the terminal enzyme of haem biosynthesis. The roles of the two enzymes in the synthesis of haem for different haemoproteins was investigated using reporter gene analysis. A 1.41 kb fragment from the 5' upstream region of the AtFC-II gene was fused to the luciferase gene, and then introduced into tobacco plants, followed by luciferase activity measurements. AtFC-II-LUCwas expressed in all aerial parts of the plant, and was highest in flowers, but it was not expressed in roots. It was unaffected by viral infection, and considerably reduced by wounding or oxidative stress. Similarly, a 1.76 kb region of the AtFC-I promoter was fused to the uidAgene encoding -glucuronidase. AtFC-I-GUS was expressed in all tissues of the plant, but was higher in roots and flowers than in leaves or stems. It was induced by sucrose, wounding and oxidative stress and, most markedly, by plants undergoing the hypersensitive response to TMV infection. Levels of endogenous ferrochelatase activity were increased in pea chloroplasts isolated from wounded leaves, indicating that the induction in promoter activity is likely to result in increased haem biosynthetic potential. Salicylic acid, but not methyl-jasmonate was able to replace the stress treatment in induction of AtFC-I expression, suggesting that the requirement for haem synthesis is part of the defence response. The implications of the results for the different roles of the two ferrochelatases in haem biosynthesis are discussed. 相似文献