全文获取类型
收费全文 | 5298篇 |
免费 | 412篇 |
国内免费 | 4篇 |
出版年
2023年 | 26篇 |
2022年 | 48篇 |
2021年 | 141篇 |
2020年 | 81篇 |
2019年 | 92篇 |
2018年 | 161篇 |
2017年 | 123篇 |
2016年 | 173篇 |
2015年 | 264篇 |
2014年 | 290篇 |
2013年 | 349篇 |
2012年 | 453篇 |
2011年 | 465篇 |
2010年 | 253篇 |
2009年 | 237篇 |
2008年 | 315篇 |
2007年 | 337篇 |
2006年 | 314篇 |
2005年 | 254篇 |
2004年 | 219篇 |
2003年 | 228篇 |
2002年 | 201篇 |
2001年 | 36篇 |
2000年 | 29篇 |
1999年 | 33篇 |
1998年 | 33篇 |
1997年 | 30篇 |
1996年 | 23篇 |
1995年 | 25篇 |
1994年 | 25篇 |
1993年 | 22篇 |
1992年 | 24篇 |
1991年 | 17篇 |
1990年 | 19篇 |
1989年 | 21篇 |
1988年 | 10篇 |
1986年 | 14篇 |
1985年 | 20篇 |
1984年 | 24篇 |
1983年 | 23篇 |
1982年 | 20篇 |
1981年 | 16篇 |
1980年 | 12篇 |
1979年 | 12篇 |
1978年 | 16篇 |
1977年 | 14篇 |
1976年 | 16篇 |
1974年 | 12篇 |
1969年 | 10篇 |
1960年 | 10篇 |
排序方式: 共有5714条查询结果,搜索用时 15 毫秒
971.
Václavíková R Boumendjel A Ehrlichová M Kovár J Gut I 《Bioorganic & medicinal chemistry》2006,14(13):4519-4525
We have investigated the effect of 13 flavonoid derivatives on [(14)C]paclitaxel transport in two human breast cancer cell lines, the adriamycin-resistant NCI/ADR-RES and sensitive MDA-MB-435. For this study, we selected representatives of aurones, chalcones, flavones, flavonols, chromones, and isoflavones with known binding affinity toward nucleotide-binding domain (NBD2) of P-glycoprotein and for which no reported work is available regarding paclitaxel transport. Aurones CB-284, CB-285, CB-287, and ML-50 most effectively inhibited P-gp related transport in the resistant line in comparison with chalcones, flavones, flavonols, chromones, and isoflavone derivatives and accordingly increased the accumulation of [(14)C]paclitaxel and decreased its efflux. Those agents efficiently modulated paclitaxel transport in P-gp highly expressing resistant human breast cancer cells and they could increase the efficiency of chemotherapy in paclitaxel-resistant tumors. In contrast, the sensitive cell line responded reversely in that CB-284, CB-285, CB-287, and ML-50 significantly inhibited accumulation of [(14)C]paclitaxel and especially CB-287, which significantly stimulated its efflux. Some, but not all, of the data correlated with the binding of flavonoid derivatives to P-gp, and indicated that even in the P-gp highly expressing NCI/ADR-RES cells, the binding was not the only factor influencing the transport of [(14)C]paclitaxel. Opposite effects of flavonoid derivatives on the P-gp highly expressing and MDA-MB-435 non-expressing cell lines indicate that paclitaxel is not only transported by P-gp and let us assume that Mrp2 or ABCC5 seem to be good transport-candidates in these cells. The inhibition of paclitaxel accumulation and stimulation of its efflux are potentially unfavorable for drug therapy and since they could be due to modulation of drug transporters other than P-gp, their expression in tumors is of great significance for efficient chemotherapy. 相似文献
972.
Mavel S Dikic B Palakas S Emond P Greguric I de Gracia AG Mattner F Garrigos M Guilloteau D Katsifis A 《Bioorganic & medicinal chemistry》2006,14(5):1599-1607
Multidrug resistance (MDR) is one of the major problems affecting the treatment of cancer. In vivo visualization and quantification of MDR proteins would be of great value to better select the therapeutic strategy. Six flavone-based compounds were synthesized and evaluated for their cytotoxic activity and MDR-reversing capacity using hMRP1 or hMDR1 overexpressing cell lines for in vitro assays. All the flavone derivatives were highly selective for hMRP1-expressing cell lines. These derivatives each used at 4muM (a non-cytotoxic concentration) enhance significantly the sensitivity of hMRP1-mediated MDR cell line toward doxorubicin toxicity. Their MDR-reversing capacity suggests that, in particular, the 4'-fluoroalkyloxy and 4'-iodo apigenin derivatives are potential new radiopharmaceuticals to visualize in vivo MRP1-mediated MDR phenomenon by PET or SPECT. 相似文献
973.
Nematodes (1 male and numerous females) of the Philometridae were collected from the mesentery of 2 species of pimelodid catfishes, Calophysus macropterus and Perrunichthys perruno, from the Amazon River basin (fishmarket in Iquitos, Loreto District) in Peru. A detailed study of their morphology (including scanning electron microscopy) and a reexamination of the type and voucher specimens of Philometra amazonica Travassos, 1960, from Brazilian catfishes confirmed that they belong to this species and that Philometra (Alinema) alii Rasheed, 1963 is its junior synonym. Because of some marked morphological peculiarities of this species (presence of minute peribuccal sclerotized formations, a functional vagina and vulva in gravid female, and structure of the male tail), the validity of an independent genus, Alinema Rasheed, 1963, is confirmed, to which this species is transferred as Alinema amazonicum (Travassos, 1960) n. comb. This is the first record of this parasite from Peru, and P. perruno represents its new host record. 相似文献
974.
R5 variants of human immunodeficiency virus type 1 preferentially infect CD62L- CD4+ T cells and are potentially resistant to nucleoside reverse transcriptase inhibitors
下载免费PDF全文
![点击此处可从《Journal of virology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
975.
976.
Semyenova SK Morozova EV Chrisanfova GG Gorokhov VV Arkhipov IA Moskvin AS Movsessyan SO Ryskov AP 《The Journal of parasitology》2006,92(3):525-530
Partial sequences of mitochondrial genes nad1 (316 bp) and cox1 (429 bp) were analyzed to estimate the variability of the liver fluke samples collected in 20 localities in Russia, Belarus, Ukraine, Bulgaria, Armenia, Azerbaijan, Georgia, Turkey, Turkmenistan, and China. The sequences had 4.1% (nad1) and 2.3% (cox1) of variable sites, and 13 and 10 haplotypes were identified among nad1 and cox1 genes, respectively. Spatial analysis of genetic and nucleotide diversity indicated little or no structuring of genetic variation between hosts or regions. The analysis of distribution of both separate and combined (nad1 + cox1) haplotypes revealed the existence of 2 well-defined lineages with 2 main haplotypes and a number of shared divergent haplotypes. Our study showed that the first lineage included the main N1-C1 haplotype, which was found in Australia, China, Georgia, Turkey, Armenia, Azerbaijan, and in all European populations (from Russia, Belarus, Ukraine, Bulgaria). The second lineage was found in all European populations and in populations from Armenia and Azerbaijan. It was suggested that one of the lineages (I) has an Asian origin. The possible source of mtDNA variability and associations between lineage divergence of parasite and its definitive hosts (cattle and sheep) are discussed. 相似文献
977.
Traditionally, the population of human embryonic stem cell (hESC) culture is estimated through haemacytometer counts, which include harvesting the cells and manually analyzing a fraction of an entire population. Obviously, through this highly invasive method, it is not possible to preserve any spatial information on the cell population. The goal of this study is to identify a fast and consistent method for in situ automated hESC population estimation to quantitatively estimate the cell growth. Therefore, cell cultures were fixed, stained, and their nuclei imaged through high‐resolution microscopy, and the images were processed with different image analysis techniques. The proposed method first identifies signal and background by computing an image specific threshold for image segmentation. By applying a morphological operator (watershed), we split most physically overlapping nuclei, leading to a pixel area distribution of isolated signal areas on the image. On the basis of this distribution, we derive a nucleus area model, describing the distribution of the area of cell debris, single nuclei, and small groups of connected nuclei. Through the model, we can give a quantitative estimation of the population. The focus of this study is on low‐density human embryonic stem cell populations; hence cultures were measured at days 2–3 after seeding. Compared with manual cell counts, the automatic method achieved higher accuracy with <6% error. © 2009 American Institute of Chemical Engineers Biotechnol. Prog., 2010 相似文献
978.
Martínková N Bačkor P Bartonička T Blažková P Cervený J Falteisek L Gaisler J Hanzal V Horáček D Hubálek Z Jahelková H Kolařík M Korytár L Kubátová A Lehotská B Lehotský R Lučan RK Májek O Matějů J Rehák Z Šafář J Tájek P Tkadlec E Uhrin M Wagner J Weinfurtová D Zima J Zukal J Horáček I 《PloS one》2010,5(11):e13853
Background
White-nose syndrome is a disease of hibernating insectivorous bats associated with the fungus Geomyces destructans. It first appeared in North America in 2006, where over a million bats died since then. In Europe, G. destructans was first identified in France in 2009. Its distribution, infection dynamics, and effects on hibernating bats in Europe are largely unknown.Methodology/Principal Findings
We screened hibernacula in the Czech Republic and Slovakia for the presence of the fungus during the winter seasons of 2008/2009 and 2009/2010. In winter 2009/2010, we found infected bats in 76 out of 98 surveyed sites, in which the majority had been previously negative. A photographic record of over 6000 hibernating bats, taken since 1994, revealed bats with fungal growths since 1995; however, the incidence of such bats increased in Myotis myotis from 2% in 2007 to 14% by 2010. Microscopic, cultivation and molecular genetic evaluations confirmed the identity of the recently sampled fungus as G. destructans, and demonstrated its continuous distribution in the studied area. At the end of the hibernation season we recorded pathologic changes in the skin of the affected bats, from which the fungus was isolated. We registered no mass mortality caused by the fungus, and the recorded population decline in the last two years of the most affected species, M. myotis, is within the population trend prediction interval.Conclusions/Significance
G. destructans was found to be widespread in the Czech Republic and Slovakia, with an epizootic incidence in bats during the most recent years. Further development of the situation urgently requires a detailed pan-European monitoring scheme. 相似文献979.
Elizabeth Buescher Tilman Achberger Idris Amusan Anthony Giannini Cherie Ochsenfeld Ana Rus Brett Lahner Owen Hoekenga Elena Yakubova Jeffrey F. Harper Mary Lou Guerinot Min Zhang David E. Salt Ivan R. Baxter 《PloS one》2010,5(6)
Controlling elemental composition is critical for plant growth and development as well as the nutrition of humans who utilize plants for food. Uncovering the genetic architecture underlying mineral ion homeostasis in plants is a critical first step towards understanding the biochemical networks that regulate a plant''s elemental composition (ionome). Natural accessions of Arabidopsis thaliana provide a rich source of genetic diversity that leads to phenotypic differences. We analyzed the concentrations of 17 different elements in 12 A. thaliana accessions and three recombinant inbred line (RIL) populations grown in several different environments using high-throughput inductively coupled plasma- mass spectroscopy (ICP-MS). Significant differences were detected between the accessions for most elements and we identified over a hundred QTLs for elemental accumulation in the RIL populations. Altering the environment the plants were grown in had a strong effect on the correlations between different elements and the QTLs controlling elemental accumulation. All ionomic data presented is publicly available at www.ionomicshub.org. 相似文献
980.
Amanda Maestre Carlos Muskus Victoria Duque Olga Agudelo Pu Liu Akihide Takagi Francis B. Ntumngia John H. Adams Kim Lee Sim Stephen L. Hoffman Giampietro Corradin Ivan D. Velez Ruobing Wang 《PloS one》2010,5(7)