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91.
Stem cells in normal breast development and breast cancer 总被引:36,自引:0,他引:36
Gabriela Dontu Muhammad Al-Hajj Wissam M. Abdallah Michael F. Clarke Max S. Wicha 《Cell proliferation》2003,36(S1):59-72
Abstract. The main focus of this review is the role of mammary stem cells in normal breast development and carcinogenesis. We have developed a new in vitro culture system that permits, for the first time, the propagation of mammary stem and progenitor cells in an undifferentiated state, which should facilitate the elucidation of pathways that regulate normal mammary stem-cell self-renewal and differentiation. Furthermore, we propose a model in which transformation of stem cells, or early progenitor cells, results in carcinogenesis. A key event in this process is the deregulation of normal self-renewal in these cells. Transformed mammary stem or progenitor cells undergo aberrant differentiation processes that result in generation of the phenotypic heterogeneity found in human and rodent breast cancers. This phenotypic diversity is driven by a small subset of mammary tumour stem cells. We will discuss the important implications of this mammary tumour stem-cell model. 相似文献
92.
Shadia A. Galal Amira S. Abd El-All Mohamed M. Abdallah Hoda I. El-Diwani 《Bioorganic & medicinal chemistry letters》2009,19(9):2420-2428
A new series of potent antitumor and antiviral benzofuran derivatives was synthesized by the reaction of the furochromone-6-carboxaldehydes 1 and 2 with different heterocyclic amines to yield the benzofuran-5-carbonyl derivatives 4–11. The synthesized compounds 1, 3–11 were tested against twelve different human cancer cell lines and all of the compounds were more potent than the comparative standards. The HIV inhibitory activity of the tested compounds 1, 3–11 showed that they have higher potency than Atevirdine. Moreover, compound 6 was significantly potent with wider therapeutic index. The HIV-1 RT inhibitory activity showed that compounds 10, 11, 3 and 4 were notably potent but with lower therapeutic index than Atevirdine. The HCV NS3-4A protease inhibitor activity of the tested compounds revealed that they have weaker potency and less therapeutic index than VX-950, although compounds 1, 4, 9 and 6, respectively exhibited significant activity. 相似文献
93.
Abdallah Said Essa Jennifer Rosenthal Kramer David Y. Graham Gerhard Treiber 《Helicobacter》2009,14(2):109-118
Background: Low success rates with triple therapy for Helicobacter pylori infections have prompted search for alternatives. In one, a proton-pump inhibitor (PPI) and amoxicillin was followed by the PPI plus clarithromycin and a nitroimidazole (sequential therapy); in another, these four drugs were given concomitantly (concomitant therapy).
Aim: To compare concomitant therapy with standard triple therapy for H. pylori infection.
Methods: By searching PubMed, EMBASE, the Cochrane Central Register of Controlled Trials and abstracts of major gastrointestinal meeting, two independent reviewers systemically identified randomized controlled trials (RCT) comparing concomitant quadruple to standard triple therapies as well as studies reporting eradication rates of concomitant quadruple therapy in treatment of H. pylori . Pooled eradication rates and odds ratios (OR) with 95% confidence intervals (CI) were calculated, and univariable metaregression analysis for all extracted variables was conducted.
Results: We identified nine studies (10 treatment arms) including five qualifying RCTs (576 subjects) comparing concomitant (293 subjects, duration 3 to 5 days) and triple therapy (283 subjects, duration 5 to 10 days) and four other studies evaluating concomitant therapy (478 subjects, duration 3 to 7 days). Pooled estimates of the five RCTs showed superiority of concomitant therapy over triple therapy; with intention-to-treat) pooled OR of 2.86 (95% CI: 1.73–4.73) and per-protocol (PP) pooled OR of 3.52 (95% CI: 1.95–6.38). Considering all 10 treatment arms, the ITT eradication rate was 89.7% (95% CI: 86.8–92.1%) and PP was 92.9% (95% CI: 90.2–94.8%).
Conclusion: Concomitant therapy appears to be an effective alternative to triple therapy and is less complex than sequential therapy. 相似文献
Aim: To compare concomitant therapy with standard triple therapy for H. pylori infection.
Methods: By searching PubMed, EMBASE, the Cochrane Central Register of Controlled Trials and abstracts of major gastrointestinal meeting, two independent reviewers systemically identified randomized controlled trials (RCT) comparing concomitant quadruple to standard triple therapies as well as studies reporting eradication rates of concomitant quadruple therapy in treatment of H. pylori . Pooled eradication rates and odds ratios (OR) with 95% confidence intervals (CI) were calculated, and univariable metaregression analysis for all extracted variables was conducted.
Results: We identified nine studies (10 treatment arms) including five qualifying RCTs (576 subjects) comparing concomitant (293 subjects, duration 3 to 5 days) and triple therapy (283 subjects, duration 5 to 10 days) and four other studies evaluating concomitant therapy (478 subjects, duration 3 to 7 days). Pooled estimates of the five RCTs showed superiority of concomitant therapy over triple therapy; with intention-to-treat) pooled OR of 2.86 (95% CI: 1.73–4.73) and per-protocol (PP) pooled OR of 3.52 (95% CI: 1.95–6.38). Considering all 10 treatment arms, the ITT eradication rate was 89.7% (95% CI: 86.8–92.1%) and PP was 92.9% (95% CI: 90.2–94.8%).
Conclusion: Concomitant therapy appears to be an effective alternative to triple therapy and is less complex than sequential therapy. 相似文献
94.
Human bone marrow derived-mesenchymal (skeletal) stem (MSC) cells are a group of non-hematopoietic stem cells residing in the perivascular niches in bone marrow. These cells have the capacity to differentiate mainly into mesoderm-type cells such as osteoblasts, chondrocytes and adipocytes and possibly but not proven to non-mesodermal cell types. Recently, there has been an increased interest in understanding the biology of MSC due to their potential use in cell-based therapy for multiple degenerative diseases. Here, we will provide an update on the current status of these novel therapeutic opportunities. J. Cell. Physiol. 218: 9-12, 2009. (c) 2008 Wiley-Liss, Inc. 相似文献
95.
Abdallah Atia Ahmed Debez Zouhaier Barhoumi Abderrazak Smaoui Chedly Abdelly 《Comptes rendus biologies》2009,332(8):704-710
Impaired germination is common among halophyte seeds exposed to salt stress, partly resulting from the salt-induced reduction of the growth regulator contents in seeds. Thus, the understanding of hormonal regulation during the germination process is a main key: (i) to overcome the mechanisms by which NaCl-salinity inhibit germination; and (ii) to improve the germination of these species when challenged with NaCl. In the present investigation, the effects of ABA, GA3, NO−3, and NH+4 on the germination of the oilseed halophyte Crithmum maritimum (Apiaceae) were assessed under NaCl-salinity (up to 200 mM NaCl). Seeds were collected from Tabarka rocky coasts (N-W of Tunisia). The exogenous application of GA3, nitrate (either as NaNO3 or KNO3), and NH4Cl enhanced germination under NaCl salinity. The beneficial impact of KNO3 on germination upon seed exposure to NaCl salinity was rather due to NO−3 than to K+, since KCl failed to significantly stimulate germination. Under optimal conditions for germination (0 mM NaCl), ABA inhibited germination over time in a dose dependent manner, but KNO3 completely restored the germination parameters. Under NaCl salinity, the application of fluridone (FLU) an inhibitor of ABA biosynthesis, stimulated substantially seed germination. Taken together, our results point out that NO−3 and GA3 mitigate the NaCl-induced reduction of seed germination, and that NO−3 counteracts the inhibitory effect of ABA on germination of C. maritimum. To cite this article: A. Atia et al., C. R. Biologies 332 (2009). 相似文献
96.
Growing investments in health research by governments and charitable organizations have fueled an increase in collaborative research projects between investigators from affluent and developing countries. Current international guidelines are silent on common intra-consortium data-sharing issues that arise in the context of such collaborations. A lack of guidance on intra-consortium data sharing threatens to undermine the success of crucial research ventures. In this work we outline some of the practical problems commonly faced by investigators working in multi-institutional, international genomic collaborations and offer recommendations on these issues. A data sharing policy should be prospectively negotiated and concluded between collaborators as early as possible. Sponsors of research, including those from developing countries, should issue detailed guidance on the above and related issues as doing so will facilitate research and catalyze scientific progress. 相似文献
97.
Berger ML Bitar AY Waitner MJ Rebernik P O'Sullivan MC 《Bioorganic & medicinal chemistry letters》2006,16(11):2837-2841
Thirty-four spermidine (SPD) and spermine (SPM) derivatives with aromatic substituents were synthesized and tested as inhibitors of specific binding of the NMDA channel blocker [3H]MK-801 to membranes prepared from rat hippocampus and cerebral cortex. SPD and SPM derivatives with aromatic substituents at the primary amino groups were the most potent inhibitors (IC50 3.9-4.7 microM). These compounds most likely act directly at the NMDA ion channel, since 30 microM SPM had no pronounced influence on their inhibiting activities. SPD derivatives with aromatic substituents at the secondary amino group were either inactive or highly SPM-sensitive inhibitors (IC50 10-82 microM), depending on the size of the substituent. Our results support the hypothesis that an aromatic interaction site near the center of polyamine derivatives contributes to polyamine inverse agonism. 相似文献
98.
Bioluminescence imaging of live infected salmonids reveals that the fin bases are the major portal of entry for Novirhabdovirus 总被引:1,自引:0,他引:1 下载免费PDF全文
Although Novirhabdovirus viruses, like the Infectious hematopietic necrosis virus (IHNV), have been extensively studied, limited knowledge exists on the route of IHNV entry during natural infection. A recombinant IHNV (rIHNV) expressing the Renilla luciferase gene was generated and used to infect trout. A noninvasive bioluminescence assay was developed so that virus replication in live fish could be followed hours after infection. We provide here evidence that the fin bases are the portal of entry into the fish. Confirmation was brought by the use of a nonpathogenic rIHNV, which was shown to persist in fins for 3 weeks postinfection. 相似文献
99.
Admixture mapping is a whole genome association strategy that takes advantage of population history-or genetic ancestry-to map genes for complex diseases. However, because it uses racial/ethnic groupings to examine differential disease risk, admixture mapping raises ethical and social concerns. While there has been much theoretical commentary regarding the ethical and social implications of population-based genetic research, empirical data from stakeholders most closely involved with these studies is limited. One of the first admixture mapping studies carried out was a scan for Multiple Sclerosis (MS) risk factors in an African-American population. Applying qualitative research methods, we used this example to explore developing views, experiences and perceptions of the ethical and social implications of admixture mapping and other population-based research-their value, risks and benefits, and the future prospects of the field. Additionally, we sought to understand how social and ethical risks might be mitigated, and the benefits of this research optimized. We draw on in-depth, one-on-one interviews with leading population geneticists, genome scientists, bioethicists, and African-Americans with MS. Here we present our findings from this unique group of key informants and stakeholders. 相似文献
100.
Johannes Fuss Nada M. B. Ben Abdallah Frank W. Hensley Klaus-Josef Weber Rainer Hellweg Peter Gass 《PloS one》2010,5(9)
Recent evidence postulates a role of hippocampal neurogenesis in anxiety behavior. Here we report that elevated levels of neurogenesis elicit increased anxiety in rodents. Mice performing voluntary wheel running displayed both highly elevated levels of neurogenesis and increased anxiety in three different anxiety-like paradigms: the open field, elevated O-maze, and dark-light box. Reducing neurogenesis by focalized irradiation of the hippocampus abolished this exercise-induced increase of anxiety, suggesting a direct implication of hippocampal neurogenesis in this phenotype. On the other hand, irradiated mice explored less frequently the lit compartment of the dark-light box test irrespective of wheel running, suggesting that irradiation per se induced anxiety as well. Thus, our data suggest that intermediate levels of neurogenesis are related to the lowest levels of anxiety. Moreover, using c-Fos immunocytochemistry as cellular activity marker, we observed significantly different induction patterns between runners and sedentary controls when exposed to a strong anxiogenic stimulus. Again, this effect was altered by irradiation. In contrast, the well-known induction of brain-derived neurotrophic factor (BDNF) by voluntary exercise was not disrupted by focal irradiation, indicating that hippocampal BDNF levels were not correlated with anxiety under our experimental conditions. In summary, our data demonstrate to our knowledge for the first time that increased neurogenesis has a causative implication in the induction of anxiety. 相似文献