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561.
Buddhi Prakash Jain Shweta Pandey Nikhat Saleem Goutam K Tanti Shalini Mishra Shyamal K. Goswami 《Cell stress & chaperones》2017,22(6):853-866
SG2NA belongs to a three-member striatin subfamily of WD40 repeat superfamily of proteins. It has multiple protein-protein interaction domains involved in assembling supramolecular signaling complexes. Earlier, we had demonstrated that there are at least five variants of SG2NA generated by alternative splicing, intron retention, and RNA editing. Such versatile and dynamic mode of regulation implicates it in tissue development. In order to shed light on its role in cell physiology, total proteome analysis was performed in NIH3T3 cells depleted of 78 kDa SG2NA, the only isoform expressing therein. A number of ER stress markers were among those modulated after knockdown of SG2NA. In cells treated with the ER stressors thapsigargin and tunicamycin, expression of SG2NA was increased at both mRNA and protein levels. The increased level of SG2NA was primarily in the mitochondria and the microsomes. A mouse injected with thapsigargin also had an increase in SG2NA in the liver but not in the brain. Cell cycle analysis suggested that while loss of SG2NA reduces the level of cyclin D1 and retains a population of cells in the G1 phase, concurrent ER stress facilitates their exit from G1 and traverse through subsequent phases with concomitant cell death. Thus, SG2NA is a component of intrinsic regulatory pathways that maintains ER homeostasis. 相似文献
562.
563.
cAR1, a G protein-coupled receptor (GPCR) for cAMP, is required for the multicellular development of Dictyostelium. The activation of multiple pathways by cAR1 is transient because of poorly defined adaptation mechanisms. To investigate this, we used a genetic screen for impaired development to isolate four dominant-negative cAR1 mutants, designated DN1-4. The mutant receptors inhibit multiple cAR1-mediated responses known to undergo adaptation. Reduced in vitro adenylyl cyclase activation by GTPgammaS suggests that they cause constitutive adaptation of this and perhaps other pathways. In addition, the DN mutants are constitutively phosphorylated, which normally requires cAMP binding and possess cAMP affinities that are approximately 100-fold higher than that of wild-type cAR1. Two independent activating mutations, L100H and I104N, were identified. These residues occupy adjacent positions near the cytoplasmic end of the receptor's third transmembrane helix and correspond to the (E/D)RY motif of numerous mammalian GPCRs, which is believed to regulate their activation. Taken together, these findings suggest that the DN mutants are constitutively activated and block development by turning on natural adaptation mechanisms. 相似文献
564.
Ridnour LA Sim JE Choi J Dickinson DA Forman HJ Ahmad IM Coleman MC Hunt CR Goswami PC Spitz DR 《Free radical biology & medicine》2005,38(10):1361-1371
Nitric oxide (*NO) is a reactive nitrogen species known to be involved in cytotoxic processes. Cells respond to cytotoxic injury by stress response induction leading to the development of cellular resistance. This report describes an *NO-induced stress response in Chinese hamster fibroblasts (HA1), which leads to glutathione synthesis-dependent resistance to H2O2-mediated oxidative stress. The development of resistance to H2O2 was completely abolished by the inhibition of glutamate cysteine ligase (GCL) during the first 8 h of recovery after *NO exposure. Altered thiol metabolism was observed immediately after *NO exposure as demonstrated by up to 75% decrease in intracellular thiol pools (glutathione, gamma-glutamylcysteine, and cysteine), which then reaccumulated during the *NO-mediated development of resistance. Immunoreactive protein and activity associated with GCL decreased immediately after exposure to *NO and then reaccumulated during the development of resistance to H2O2 challenge. Moreover, compared to N2 controls the activity levels of GCL in *NO-exposed cells increased approximately twofold 24 h after H2O2 challenge. These results demonstrate that *NO exposure is capable of inducing an adaptive response to H2O2-mediated oxidative stress in mammalian cells, which involves alterations in thiol metabolism and is dependent upon glutathione synthesis and increased GCL activity. 相似文献
565.
Chakravarty BN Shirazee HH Dam P Goswami SK Chatterjee R Ghosh S 《The Journal of steroid biochemistry and molecular biology》2005,97(5):416-420
The objective of this prospective, randomised study was to compare the efficacy, safety and tolerability of vaginal micronised progesterone with oral dydrogesterone as luteal phase support after in-vitro fertilisation (IVF). A total of 430 women underwent IVF/intracytoplasmic sperm injection (ICSI) treatment. Long protocol gonadotropin releasing hormone analogue down-regulation was followed by gonadotropin stimulation. Human chorionic gonadotropin was given when two or more follicles reached ≥17 mm. After 36 h, oocytes were retrieved and IVF was performed. Embryo transfer was done at the 4–8 cell embryo stage. Luteal support was initiated from the day of embryo transfer and continued for up to 14 days. Patients were randomised to luteal supplementation with either intravaginal micronised progesterone 200 mg three times daily (n = 351) or oral dydrogesterone 10 mg twice daily (n = 79). In cases of a positive pregnancy test, luteal support was continued for 12 weeks. Both dydrogesterone and micronised progesterone were associated with similar rates of successful pregnancies. Vaginal discharge or irritation were reported by 10.5% of patients given micronised progesterone. Significantly (p < 0.05), more patients given dydrogesterone than micronised progesterone were satisfied with the tolerability of their treatment. There were no differences between the treatments with regard to liver function tests. 相似文献
566.
Wang W Goswami S Sahai E Wyckoff JB Segall JE Condeelis JS 《Trends in cell biology》2005,15(3):138-145
Invasion of neighboring extracellular matrix tissue, the lymphatic system and blood vessels is a key element of tumor cell metastasis in many epithelial tumors. Understanding the cell motility pathways that contribute to invasion can provide new approaches and targets for anticancer therapy. The recent convergence of technologies for expression profiling and intravital imaging has revealed the identities of some of the genes that contribute to motility and chemotaxis of cancer cells in tumors. In particular, the genes encoding a minimum motility machine are coordinately upregulated in tumor cells collected by an in vivo invasion assay. These results support a "tumor microenvironment invasion model" and provide new target opportunities for cancer therapy. 相似文献
567.
Manganese superoxide dismutase protects the proliferative capacity of confluent normal human fibroblasts 总被引:2,自引:0,他引:2
Sarsour EH Agarwal M Pandita TK Oberley LW Goswami PC 《The Journal of biological chemistry》2005,280(18):18033-18041
We tested the hypothesis that manganese superoxide dismutase (MnSOD), an antioxidant enzyme, regulates the proliferative potential of confluent human fibroblasts. Normal human skin (AG01522) and lung (WI38, CCL-75) fibroblasts kept in confluence (>95% G(0)/G(1)) showed a significant decrease in their capacity to re-enter the proliferation cycle after 40-60 days. The inhibition of re-entry was accompanied with the age-dependent increase of p16 protein levels in the confluent culture. Adenoviral mediated overexpression of MnSOD during confluent growth suppressed p16, enhanced p21 protein accumulation, and protected fibroblasts against the loss of proliferation potential. Increases in p21 protein levels in MnSOD overexpressing confluent fibroblasts were independent of p53 protein levels. p53 protein levels did not change in control, replication-defective adenovirus containing an insertless vector (AdBgl II), or AdMnSOD-infected confluent cells cultured for 20 and 60 days. In addition, MnSOD-induced protection of the proliferation capacity of confluent fibroblasts was independent of their telomerase activity. However, telomerase-transformed fibroblasts showed increased MnSOD expression in confluent growth, maintaining their capacity to re-enter the proliferation cycle. Although inactivation of the retinoblastoma protein in cells subcultured from the 60-day confluent control, AdBgl II-, and AdMnSOD-infected fibroblasts was identical, only MnSOD-overexpressing cells showed a higher percentage of S-phase. These results support the hypothesis that a redox-sensitive checkpoint regulated the progression of fibroblasts from G(0)/G(1) to S-phase. 相似文献
568.
Chowdhury AR Mandal S Goswami A Ghosh M Mandal L Chakraborty D Ganguly A Tripathi G Mukhopadhyay S Bandyopadhyay S Majumder HK 《Molecular medicine (Cambridge, Mass.)》2003,9(1-2):26-36
Leishmaniasis is the second-most dreaded parasitic disease in the modern world, behind malaria. The lack of effective vaccines demand improved chemotherapy along with the development of lead compounds and newer targets. We report here that the pentacyclic triterpenoid, dihydrobetulinic acid (DHBA), is a novel lead compound for antileishmanial therapy. It acts by targeting DNA topoisomerases. DNA topoisomerase I and II activity was studied using relaxation and decatenation assays. Mechanistic studies were based on the decreased mobility of enzyme-bound DNA compared with free DNA and the differential mobility of nicked and supercoiled monomers in 1% agarose gel. Pulsed field gradient gel electrophoresis, confocal microscopy, and transmission electron microscopy were performed to assess cytotoxicity of the compound and ultrastructural damage of the parasite. Apoptosis was studied by the isolation of DNA from DHBA-treated parasites and subsequent electrophoresis in 1% agarose gel. DHBA inhibits growth of Leishmania donovani promastigotes and amastigotes with an IC50 of 2.6 and 4.1 microM respectively. The compound is a dual inhibitor of DNA topoisomerases that fails to induce DNA cleavage and acts by preventing the formation of enzyme-DNA binary complex, ultimately inducing apoptosis. Treatment of infected golden hamsters with the compound markedly reduces (> 92%) parasitic burden, both in spleen and liver. Interestingly, the 17-decarboxylated analogue, dihydrolupeol, does not inhibit DNA topoisomerase I and II, has no effect on parasitic growth, and also fails to induce apoptosis. DHBA is a potent antileishmanial agent that induces apoptosis by primarily targeting DNA topoisomerases. Therefore it is a strong candidate for use in designing new antileishmanial drugs. 相似文献
569.
Effects of plant hormones indole-3-yl-acetic acid (IAA), gibberellic acid (GA), benzylaminopurine (BAP), abscisic acid (ABA) and ethrel (ETH) in 5 M concentration on gas exchange, ribulose-1,5-bisphosphate carboxylase/oxygenase (RuBPCO, EC 4.1.1.39) activity, pigment content and yield in cotton (Gossypium hirsutum L. cv. H-777) under drought were studied. At reproductive stage (55 – 60 d after sowing) these hormones were sprayed on shoots one day prior to stress imposition by withholding irrigation. The soil moisture of control plants was kept at field capacity. Net photosynthetic rate (PN), stomatal conductance (gs), transpiration rate (E), carboxylation efficiency (CE), water use efficiency (WUE), RuBPCO activity, boll number per plant, seed number per plant and lint mass per plant significantly decreased at drought while chlorophyll (Chl) b content and flower number per plant increased. ABA and ETH significantly reduced gas exchange parameters, Chl a and Chl b content. Detrimental drought effect on PN, gs, E, CE, RuBPCO and lint mass per plant was significantly alleviated by BAP and also its effect on seed number and lint mass per plant was significantly alleviated with the ABA treatment. 相似文献
570.