全文获取类型
收费全文 | 233篇 |
免费 | 12篇 |
专业分类
245篇 |
出版年
2021年 | 4篇 |
2019年 | 2篇 |
2018年 | 2篇 |
2017年 | 3篇 |
2015年 | 3篇 |
2014年 | 5篇 |
2013年 | 5篇 |
2012年 | 12篇 |
2011年 | 11篇 |
2010年 | 12篇 |
2009年 | 8篇 |
2008年 | 8篇 |
2007年 | 10篇 |
2006年 | 5篇 |
2005年 | 6篇 |
2004年 | 3篇 |
2003年 | 16篇 |
2002年 | 4篇 |
2001年 | 5篇 |
2000年 | 3篇 |
1999年 | 6篇 |
1998年 | 2篇 |
1997年 | 3篇 |
1996年 | 2篇 |
1995年 | 4篇 |
1994年 | 7篇 |
1992年 | 5篇 |
1991年 | 7篇 |
1990年 | 2篇 |
1989年 | 3篇 |
1988年 | 5篇 |
1987年 | 4篇 |
1986年 | 4篇 |
1985年 | 6篇 |
1983年 | 4篇 |
1982年 | 4篇 |
1980年 | 3篇 |
1979年 | 2篇 |
1978年 | 2篇 |
1977年 | 3篇 |
1974年 | 4篇 |
1972年 | 3篇 |
1971年 | 3篇 |
1970年 | 5篇 |
1969年 | 8篇 |
1968年 | 4篇 |
1952年 | 1篇 |
1940年 | 1篇 |
1939年 | 2篇 |
1936年 | 1篇 |
排序方式: 共有245条查询结果,搜索用时 15 毫秒
1.
Feces from 15 dogs at 2 different foxhound kennels in the U.K. were examined microscopically for the presence of oocysts of Neospora caninum. One sample containing approximately 400 candidate oocysts per gram was positive in a polymerase chain reaction (PCR) using N. caninum-specific primers. In a sample taken 4 mo later from the same hound. N. caninum oocysts were again detected visually and by PCR. This is the third reported case of a dog naturally excreting oocysts of N. caninum and suggests that oocyst excretion can occur over a relatively long period of time in some circumstances or that reshedding may occur. 相似文献
2.
3.
Sara El-Sahli Khang Hua Andrew Sulaiman Jason Chambers Li Li Eliya Farah Sarah McGarry Dan Liu Peiyong Zheng Seung-Hwan Lee Jiefeng Cui Marc Ekker Marceline Ct Tommy Alain Xuguang Li Vanessa M. DCosta Lisheng Wang Suresh Gadde 《Cell death & disease》2021,12(1)
Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer, accounting for the majority of breast cancer-related death. Due to the lack of specific therapeutic targets, chemotherapeutic agents (e.g., paclitaxel) remain the mainstay of systemic treatment, but enrich a subpopulation of cells with tumor-initiating capacity and stem-like characteristics called cancer stem cells (CSCs); thus development of a new and effective strategy for TNBC treatment is an unmet medical need. Cancer nanomedicine has transformed the landscape of cancer drug development, allowing for a high therapeutic index. In this study, we developed a new therapy by co-encapsulating clinically approved drugs, such as paclitaxel, verteporfin, and combretastatin (CA4) in polymer-lipid hybrid nanoparticles (NPs) made of FDA-approved biomaterials. Verteporfin is a drug used in the treatment of macular degeneration and has recently been found to inhibit the Hippo/YAP (Yes-associated protein) pathway, which is known to promote the progression of breast cancer and the development of CSCs. CA4 is a vascular disrupting agent and has been tested in phase II/III of clinical trials. We found that our new three drug-NP not only effectively inhibited TNBC cell viability and cell migration, but also significantly diminished paclitaxel-induced and/or CA4-induced CSC enrichment in TNBC cells, partially through inhibiting the upregulated Hippo/YAP signaling. Combination of verteporfin and CA4 was also more effective in suppressing angiogenesis in an in vivo zebrafish model than single drug alone. The efficacy and application potential of our triple drug-NPs were further assessed by using clinically relevant patient-derived xenograft (PDX) models. Triple drug-NP effectively inhibited the viability of PDX organotypic slide cultures ex vivo and stopped the growth of PDX tumors in vivo. This study developed an approach capable of simultaneously inhibiting bulk cancer cells, CSCs, and angiogenesis.Subject terms: Breast cancer, Cancer stem cells 相似文献
4.
CK Bower J McGuire MA Daeschel 《Journal of industrial microbiology & biotechnology》1995,15(3):227-233
The efficacy of the antimicrobial peptide nisin was examined after adsorption to silica surfaces. Three protocols were used to evaluate nisin's activity against adhered cells ofListeria monocytogenes: bioassay usingPediococcus pentosaceous FBB 61-2 as the sensitive indicator strain; visualization and enumeration of cells by microscopic image analysis; and viability of adhered cells as determined by lodonitrotetrazolium violet uptake and crystallization. The activity of adsorbed nisin was highly dependent upon conditions of adsorption. The highest antimicrobial activity of adsorbed nisin occurred with high concentrations of nisin (1.0 mg ml–1) and brief contact times (1 h) on surfaces of low hydrophobicity. Sequential adsorption of a second protein (-lactoglobulin or bovine serum albumin) onto surfaces consistently resulted in decreased nisin activity. These data provide direction for the development of applications to limit microbial attachment on food contact surfaces through the use of adsorbed antimicrobial peptides. 相似文献
5.
G L Picciolo E W Chappelle R R Thomas M A McGarry 《Applied and environmental microbiology》1977,34(6):720-724
The performance characteristics of a new photometer that incorporated a reaction system consisting of a movable filtration tape have been studied for use with the firefly luciferase assay for adenosine 5'-triphosphate. Precision, linearity, and sensitivity are given for measuring a graded series of constant-light emitters, concentrations of adenosine 5'-triphosphate, and washed bacterial cells. Precision ranged from 1 to 10% coefficient of variation. The coefficient of correlation was 0.9985 for 7 X 10(8) to 7 X 10(3) bacteria per ml; however, the accuracy decreased at the low levels. The sample processing time was 2 min for a 1-ml sample. This instrument shows potential for many applications in quantitating small numbers of organisms, e.g., pollution, water monitoring, and clinical infection detection. 相似文献
6.
7.
Eui-Ju Hong Se-Hyung Park Kyung-Chul Choi Peter CK Leung Eui-Bae Jeung 《Reproductive biology and endocrinology : RB&E》2006,4(1):49-12
Environmental estrogenic compounds which bind to the estrogen receptor (ER) can block or alter endogenous functions of estrogen
in reproductive and developmental stages. A microarray technology is a very valuable method for the prediction of hormone-responsive
activities in various gene expressions. Thus, we investigated the altered gene expression by estrogen and endocrine disruptors
(EDs) using microarray technology in the uterus of immature rats. In this study, the expression levels of only 555 genes (7.42%)
among the 7636 genes spotted on microarray chips were enhanced by more than two-fold following treatment with estradiol (E2),
suggesting that direct or rapid response to E2 is widespread at the mRNA levels in these genes. In addition, elevated expression
levels of the genes (over 2-fold) were observed by diethylstilbestrol (DES; 9.01%), octyl-phenol (OP; 8.81%), nonyl-phenol
(NP; 9.51%), bisphenol-A (BPA; 8.26%) or genistein (9.97%) in the uterus of immature rats. The expression levels of representative
genes, i.e., calbindin-D9k (CaBP-9k; vitamin D-dependent calcium-binding protein), oxytocin, adipocyte complement related
protein (MW 30 kDa), lactate dehydrogenase A and calcium binding protein A6 (S100a6; calcyclin), were confirmed in these tissues
by real-time PCR. In addition, the mRNA levels of these genes by real-time PCR were increased at follicular phase when E2
level was elevated during estrous cycle of adult female rats. In conclusion, these results indicate distinct altered expression
of responsive genes following exposure to E2 and estrogenic compounds, and implicate distinct effects of endogenous E2 and
environmental endocrine disrupting chemicals in the uterus of immature rats. 相似文献
8.
Angela M. Tavolieri Daniel T. Murray Isabel Askenasy Joseph M. Pennington Lauren McGarry Christopher B. Stanley M. Elizabeth Stroupe 《Journal of structural biology》2019,205(2):170-179
This is the first X-ray crystal structure of the monomeric form of sulfite reductase (SiR) flavoprotein (SiRFP-60) that shows the relationship between its major domains in an extended position not seen before in any homologous diflavin reductases. Small angle neutron scattering confirms this novel domain orientation also occurs in solution. Activity measurements of SiR and SiRFP variants allow us to propose a novel mechanism for electron transfer from the SiRFP reductase subunit to its oxidase metalloenzyme partner that, together, make up the SiR holoenzyme. Specifically, we propose that SiR performs its 6-electron reduction via intramolecular or intermolecular electron transfer. Our model explains both the significance of the stoichiometric mismatch between reductase and oxidase subunits in the holoenzyme and how SiR can handle such a large volume electron reduction reaction that is at the heart of the sulfur bio-geo cycle. 相似文献
9.
Marlene Neethling Conrad A Matthee Rauri CK Bowie Sophie von der Heyden 《BMC evolutionary biology》2008,8(1):325
Background
Oceanography and life-history characteristics are known to influence the genetic structure of marine species, however the relative role that these factors play in shaping phylogeographic patterns remains unresolved. The population genetic structure of the endemic, rocky shore dwelling Caffrogobius caffer was investigated across a known major oceanographic barrier, Cape Agulhas, which has previously been shown to strongly influence genetic structuring of South African rocky shore and intertidal marine organisms. Given the variable and dynamic oceanographical features of the region, we further sought to test how the pattern of gene flow between C. caffer populations is affected by the dominant Agulhas and Benguela current systems of the southern oceans. 相似文献10.
CAROLINE BETTO‐COLLIARD MATTHIAS STÖCK 《Biological journal of the Linnean Society. Linnean Society of London》2012,105(3):584-590
In vertebrates, genome size has been shown to correlate with nuclear and cell sizes, and influences phenotypic features, such as brain complexity. In three different anuran families, advertisement calls of polyploids exhibit longer notes and intervals than diploids, and difference in cellular dimensions have been hypothesized to cause these modifications. We investigated this phenomenon in green toads (Bufo viridis subgroup) of three ploidy levels, in a different call type (release calls) that may evolve independently from advertisement calls, examining 1205 calls, from ten species, subspecies, and hybrid forms. Significant differences between pulse rates of six diploid and four polyploid (3n, 4n) green toad forms across a range of temperatures from 7 to 27 °C were found. Laboratory data supported differences in pulse rates of triploids vs. tetraploids, but failed to reach significance when including field recordings. This study supports the idea that genome size, irrespective of call type, phylogenetic context, and geographical background, might affect call properties in anurans and suggests a common principle governing this relationship. The nuclear‐cell size ratio, affected by genome size, seems the most plausible explanation. However, we cannot rule out hypotheses under which call‐influencing genes from an unexamined diploid ancestral species might also affect call properties in the hybrid‐origin polyploids. © 2012 The Linnean Society of London, Biological Journal of the Linnean Society, 2012, 105 , 584–590. 相似文献