全文获取类型
收费全文 | 516篇 |
免费 | 22篇 |
国内免费 | 1篇 |
出版年
2023年 | 8篇 |
2022年 | 12篇 |
2021年 | 35篇 |
2020年 | 17篇 |
2019年 | 20篇 |
2018年 | 22篇 |
2017年 | 11篇 |
2016年 | 19篇 |
2015年 | 21篇 |
2014年 | 23篇 |
2013年 | 35篇 |
2012年 | 32篇 |
2011年 | 31篇 |
2010年 | 23篇 |
2009年 | 12篇 |
2008年 | 19篇 |
2007年 | 35篇 |
2006年 | 22篇 |
2005年 | 24篇 |
2004年 | 16篇 |
2003年 | 9篇 |
2002年 | 11篇 |
2001年 | 8篇 |
2000年 | 9篇 |
1999年 | 4篇 |
1994年 | 2篇 |
1993年 | 3篇 |
1992年 | 4篇 |
1991年 | 1篇 |
1990年 | 4篇 |
1989年 | 2篇 |
1988年 | 2篇 |
1987年 | 3篇 |
1986年 | 1篇 |
1985年 | 2篇 |
1981年 | 1篇 |
1980年 | 2篇 |
1978年 | 1篇 |
1977年 | 3篇 |
1976年 | 2篇 |
1975年 | 4篇 |
1974年 | 3篇 |
1973年 | 5篇 |
1972年 | 3篇 |
1971年 | 1篇 |
1969年 | 1篇 |
1968年 | 3篇 |
1967年 | 3篇 |
1966年 | 2篇 |
1961年 | 1篇 |
排序方式: 共有539条查询结果,搜索用时 15 毫秒
171.
Aklima Nargis Harun-Or-Rashid Anowara Khanam Jhumur Md Easin Haque Md Nazrul Islam 《人类与生态风险评估》2020,26(1):120-146
AbstractMultielement (48) analysis was carried out of various fish species collected from river Buriganga, the most polluted river in Bangladesh to assess human health risk by toxic elements. Sixteen elements that is, Be, V, Cr, Mn, Ni, Cu, Zn, As, Se, Mo, Cd, Ba, Hg, Pb, Bi, and U, were taken into account due to their toxicities on human health. Results show that concentrations of elements in various fish species were higher in winter than those in monsoon. Among 16 elements, Mn, Cu, Zn, Cd, Ba, Pb were above Food Safety Guideline in some fishes in winter. THQ and TTHQ/HI values were less than 1 for all fishes in monsoon while THQ and TTHW/HI values were more than 1 for most of fishes in winter. These results suggesting non-carcinogenic health hazard through consumption of contaminated fishes. Only As showed low cancer risk while no cancer risk was observed for other toxic elements in monsoon. In winter, Pb showed only moderate cancer risk for Mystus vittatus (site-7) while for other fishes low cancer risk was found by Pb. It can therefore be concluded that there is human health risk in consuming of fishes collected from river Buriganga especially in winter. 相似文献
172.
Several studies have documented contamination levels and daily intake of metallic elements from foodstuffs including rice, maize, pulses, vegetables, fruits, fish, meat, egg, milk etc., however, limited literature is available on metal contamination levels in wild growing mushrooms and possible human exposure via consumption of it. Sarcodon imbricatus is an edible mushroom, commonly consumed in many parts of the world. Very few studies have been conducted on inorganic elemental composition in fruiting bodies (edible part) of this fungus. In this study, elements such as silver (Ag), aluminum (Al), barium (Ba), calcium (Ca), cadmium (Cd), cobalt (Co,) chromium (Cr), copper (Cu), iron (Fe), mercury (Hg), potassium (K), magnesium (Mg), manganese (Mn), sodium (Na), nickel (Ni), phosphorous (P), lead (Pb), rubidium (Rb), strontium (Sr) and zinc (Zn) were measured in caps and stems of fruiting bodies of S. imbricatus collected from the Wdzydze forests in Central and the Augustowska Primeval forest in Eastern Poland. Results revealed that a wide variation in concentrations of various metals in caps and stems samples collected from the two forests. Toxic metallic elements such as Cd and Hg showed preferential accumulation in caps than stems samples from both the forests. However, the concentrations of Cd, Hg and Pb in the mushroom samples were below the established weekly intake tolerance limits. 相似文献
173.
Carmelo Carlo-Stella Silvia L. Locatelli Arianna Giacomini Loredana Cleris Elena Saba Marco Righi Anna Guidetti Alessandro M. Gianni 《PloS one》2013,8(4)
The anti-lymphoma activity and mechanism(s) of action of the multikinase inhibitor sorafenib were investigated using a panel of lymphoma cell lines, including SU-DHL-4V, Granta-519, HD-MyZ, and KMS-11 cell lines. In vitro, sorafenib significantly decreased cell proliferation and phosphorylation levels of MAPK and PI3K/Akt pathways while increased apoptotic cell death. In vivo, sorafenib treatment resulted in a cytostatic rather than cytotoxic effect on tumor cell growth associated with a limited inhibition of tumor volumes. However, sorafenib induced an average 50% reduction of tumor vessel density and a 2-fold increase of necrotic areas. Upon sorafenib treatment, endothelial and tumor cells from SU-DHL-4V, Granta-519, and KMS-11 nodules showed a potent inhibition of either phospho-ERK or phospho-AKT, whereas a concomitant inhibition of phospho-ERK and phospho-AKT was only observed in HD-MyZ nodules. In conclusion, sorafenib affects the growth of lymphoid cell lines by triggering antiangiogenic mechanism(s) and directly targeting tumor cells. 相似文献
174.
Richelle C. Charles Tania Sultana Mohammad Murshid Alam Yanan Yu Ying Wu-Freeman Meagan Kelly Bufano Sean M. Rollins Lillian Tsai Jason B. Harris Regina C. LaRocque Daniel T. Leung W. Abdullah Brooks Tran Vu Thieu Nga Sabina Dongol Buddha Basnyat Stephen B. Calderwood Jeremy Farrar Farhana Khanam John S. Gunn Firdausi Qadri Stephen Baker Edward T. Ryan 《PLoS neglected tropical diseases》2013,7(8)
Background
Salmonella enterica serotype Typhi can colonize and persist in the biliary tract of infected individuals, resulting in a state of asymptomatic chronic carriage. Chronic carriers may act as persistent reservoirs of infection within a community and may introduce infection to susceptible individuals and new communities. Little is known about the interaction between the host and pathogen in the biliary tract of chronic carriers, and there is currently no reliable diagnostic assay to identify asymptomatic S. Typhi carriage.Methodology/Principal Findings
To study host-pathogen interactions in the biliary tract during S. Typhi carriage, we applied an immunoscreening technique called in vivo-induced antigen technology (IVIAT), to identify potential biomarkers unique to carriers. IVIAT identifies humorally immunogenic bacterial antigens expressed uniquely in the in vivo environment, and we hypothesized that S. Typhi surviving in the biliary tract of humans may express a distinct antigenic profile. Thirteen S. Typhi antigens that were immunoreactive in carriers, but not in healthy individuals from a typhoid endemic area, were identified. The identified antigens included a number of putative membrane proteins, lipoproteins, and hemolysin-related proteins. YncE (STY1479), an uncharacterized protein with an ATP-binding motif, gave prominent responses in our screen. The response to YncE in patients whose biliary tract contained S. Typhi was compared to responses in patients whose biliary tract did not contain S. Typhi, patients with acute typhoid fever, and healthy controls residing in a typhoid endemic area. Seven of 10 (70%) chronic carriers, 0 of 8 bile culture-negative controls (0%), 0 of 8 healthy Bangladeshis (0%), and 1 of 8 (12.5%) Bangladeshis with acute typhoid fever had detectable anti-YncE IgG in blood. IgA responses were also present.Conclusions/Significance
Further evaluation of YncE and other antigens identified by IVIAT could lead to the development of improved diagnostic assays to identify asymptomatic S. Typhi carriers. 相似文献175.
Edwin Kamau Saba Alemayehu Karla C. Feghali David Saunders Christian F. Ockenhouse 《PloS one》2013,8(8)
We describe development of an absolute multiplex quantitative real-time PCR for detection of Plasmodium spp., P. falciparum and P. vivax targets in order to produce an assay amenable to high throughput but with reduced costs. Important qPCR experimental details and information that is critical to performance and reliability of assay results were investigated. Inhibition studies were performed to test and compare co-purification of PCR inhibitors in samples extracted from whole blood using either the manual or automated methods. To establish the most optimal qPCR reaction volume, volume titration of the reaction master mix was performed starting at 10 µl to 1 µl reaction master mix with 1 µl of template DNA in each reaction. As the reaction volume decreased, qPCR assays became more efficient with 1 µl reaction master mix being the most efficient. For more accurate quantification of parasites in a sample, we developed plasmid DNAs for all the three assay targets for absolute quantification. All of absolute qPCR assays performed with efficiency of more than 94%, R2 values greater than 0.99 and the STDEV of each replicate was <0.167. Linear regression plots generated from absolute qPCR assays were used to estimate the corresponding parasite density from relative qPCR in terms of parasite/µl. One copy of plasmid DNA was established to be equivalent to 0.1 parasite/µl for Plasmodium spp. assay, 0.281 parasites for P. falciparum assay and 0.127 parasite/µl for P. vivax assay. This study demonstrates for the first time use of plasmid DNA in absolute quantification of malaria parasite. The use of plasmid DNA standard in quantification of malaria parasite will be critical as efforts are underway to harmonize molecular assays used in diagnosis of malaria. 相似文献
176.
This paper examines the impact of childhood malnutrition on schooling performance in rural Bangladesh. The results reveal that malnourished children are less likely to enrol in school on time and achieve an age-appropriate grade by 26 percentage points and 31 percentage points, respectively. Other important determinants of schooling outcomes include infrastructure and education level of parents. One major contribution of this paper is the control for the endogeneity of malnutrition status, which otherwise might lead to bias estimates. 相似文献
177.
Ligios C Cancedda MG Carta A Santucciu C Maestrale C Demontis F Saba M Patta C DeMartini JC Aguzzi A Sigurdson CJ 《Journal of virology》2011,85(2):1136-1139
Prions are misfolded proteins that are infectious and naturally transmitted, causing a fatal neurological disease in humans and animals. Prion shedding routes have been shown to be modified by inflammation in excretory organs, such as the kidney. Here, we show that sheep with scrapie and lentiviral mastitis secrete prions into the milk and infect nearly 90% of naïve suckling lambs. Thus, lentiviruses may enhance prion transmission, conceivably sustaining prion infections in flocks for generations. This study also indicates a risk of prion spread to sheep and potentially to other animals through dietary exposure to pooled sheep milk or milk products.Prion diseases have emerged globally as a significant threat to human and animal health. Recently, human-to-human spread of prions is believed to have occurred through blood transfusions (9, 12, 16), underscoring the importance of understanding possible transmission routes. PrPSc, a misfolded, aggregated form of the normal prion protein, PrPC, commonly accumulates in the follicles of lymphoid tissues, prior to entering the central nervous system (2, 11, 14). Inflammation can cause lymphoid follicles to form in other organs, such as liver and kidney, which leads to prion invasion of organs that are not typically prion permissive (1). In mice, prion infection in the inflamed kidney has the untoward consequence of prion excretion in urine (13). This finding, together with our report of sheep with PrPSc in the inflamed mammary gland (8), has raised concerns of prion secretion into milk.Here, we investigated whether PrPSc in the inflamed mammary gland leads to prion secretion in milk and infection of naïve lambs through suckling. Prion infectivity has been detected in the milk of sheep expressing a prion gene (Prnp) coding for VRQ/VRQ or VRQ/ARQ at polymorphic codons 136, 154, and 171 (3, 4). However, whether (i) sheep-to-lamb transmission of prions in milk leads to clinical prion disease or (ii) sheep with the common ARQ/ARQ Prnp genotype can infect lambs through milk is unknown. We induced a chronic lentiviral mastitis and inoculated ARQ/ARQ Sarda breed sheep with infectious prions. After 14 months, we bred the sheep and collected the milk. To avoid cross-contamination of newborn lambs, we fed the milk to imported known-naïve lambs and then monitored the lambs for signs of prion infection (Fig. (Fig.1A1A).Open in a separate windowFIG. 1.Sheep infected with prions and maedi-visna virus (MVV) develop lymphofollicular mastitis with PrPSc. (A) Experimental scheme. Sheep were inoculated with culture medium or MVV and were then orally exposed to scrapie prions and bred. Milk was collected near the time point that neurologic signs of scrapie developed and was fed to naïve lambs. The ratio of lambs with detectable PrPSc to lambs fed the indicated milk is shown for each experiment. (B) PrP immunohistochemistry assay of brain and tonsil from milk source sheep shows staining for PrPSc in the brainstem, particularly in the vagal nucleus (indicated by asterisks) and in the tonsillar follicles of scrapie-infected sheep (arrows). (C) Mammary gland (MG) of milk source sheep shows lymphoid follicles (arrowheads) with associated PrPSc (arrows) adjacent to milk ducts (md) in the MVV-inoculated sheep, whereas the medium-inoculated sheep had a histologically normal MG with no detectable PrPSc. Insets show a high magnification of follicles containing PrPSc. Scale bar = 100 μm; scale bar in inset = 25 μm. (D) Western blot analysis shows PrPSc detection in MG of sheep inoculated with MVV/scrapie agents but not in sheep inoculated with scrapie prions only. The sheep identification number is indicated for each lane. PK, proteinase K digested; pos. br, positive brain control; neg. br, negative brain control.To induce a chronic lymphofollicular mastitis, we exposed 7- to 10-day-old lambs (groups of 10) by intratracheal and intravenous routes to a common sheep lentivirus known as maedi-visna virus (MVV) or to cell culture medium only. To do this, lambs were inoculated with 3.5 ml intravenously and 0.5 ml intratracheally of MVV in culture supernatant containing 1.5 × 106 tissue culture infectious doses/ml of the “rapid/high” MVV strain 85/34 (5, 15). Twenty days later, all lambs were orally inoculated with 25 ml of 10% scrapie-infected brain homogenate from a pool of naturally infected Sarda sheep.We sequenced the entire Prnp gene and found that all lambs expressed the ARQ/ARQ Prnp genotype, indicating that the sheep should be susceptible to scrapie. As negative controls, 2 lambs of Prnp genotype ARR/ARR and ARQ/ARQ were mock inoculated with cell culture medium and healthy brain homogenate. All lambs originated from scrapie-free flocks that had been monitored for clinical scrapie cases for at least 3 years.All inoculated sheep were naturally bred to rams at 15 months postinoculation (p.i.) and produced lambs at 20 months p.i. Sheep developed early signs of scrapie just after the lambs were born. Milk from each sheep was manually collected and frozen daily.Eight of 10 MVV-and-scrapie (denoted MVV/scrapie)-inoculated sheep and 9 of 10 scrapie-inoculated sheep showed clinical signs of scrapie, with mean incubation periods of 22 ± 1.4 and 23 ± 1.5 months postinoculation, respectively, and were euthanized. There was no significant difference in incubation period between the groups (Student''s t test, P = 0.5), indicating that inflammation associated with the MVV infection does not accelerate prion disease. This finding is consistent with the results of previous studies that showed that chronic pancreatitis or nephritis did not affect the scrapie incubation period (1). Scrapie infection was confirmed postmortem by the detection of PrPSc in brain and lymphoid tissues by Western blot and immunohistochemistry assays (Fig. (Fig.1B).1B). Interestingly, scrapie did not develop in 3 sheep with a Prnp gene encoding a rare polymorphism at codon 176 (K), consistent with recent reports describing scrapie resistance for this genotype (10).Antibodies to MVV were detected in serum of all the MVV-inoculated sheep by indirect enzyme-linked immunosorbent assay (ELISA) (Elitest kit; Hyphen BioMed). Five of 8 MVV/scrapie-infected sheep (63%) showed a lymphofollicular mastitis (Fig. (Fig.1C),1C), and 3 had a diffuse interacinar lymphoid infiltrate. Of the 5 sheep with lymphofollicular mastitis, 4 had PrPSc deposits detectable by immunohistochemistry and Western blot assays (Fig. 1C and D), whereas no sheep with diffuse lymphoid infiltrates had detectable PrPSc. Surprisingly, 2 of 9 sheep inoculated only with scrapie also had lymphofollicular mastitis and anti-MVV antibodies, one of which had visible PrPSc deposits. MVV is a common pathogen in Europe, and it is possible that these sheep were infected from the dam. The remaining 7 scrapie-inoculated sheep had histologically normal mammary glands (Fig. (Fig.1C)1C) and no detectable PrPSc (Fig. (Fig.1D)1D) or anti-MVV antibodies.We selected the stored milk from the 4 MVV/scrapie-infected sheep with PrPSc in the mammary glands and from the 7 scrapie-infected sheep with histologically normal mammary glands. Milk samples from the early, middle, and late stages of lactation were pooled for each group. We imported naïve Cheviot lambs (n = 9) from flocks that originated from scrapie-free New Zealand and had been bred and housed under strict biosecurity containment in the United Kingdom to ensure that the lambs had not been exposed to scrapie. The Sarda lambs (n = 4) originated from a scrapie-free flock in Sardinia. We then fed pooled milk from MVV/scrapie-infected sheep to each of 8 naïve ARQ/ARQ lambs and from scrapie-infected sheep to 3 naïve ARQ/ARQ lambs ad libitum. Each lamb ingested a total volume of 1 to 2 liters over a total period of 3 days (Table (Table1).1). Two lambs were orally inoculated with brain homogenate pooled from the scrapie-infected milk donors as positive controls. Groups of lambs were housed in separate stalls and subjected to isolation conditions.
Open in a separate windowaThe Prnp genotype of all lambs was ARQ/ARQ at codons 136, 154, and 171. Additional dimorphisms in other codons of Prnp are noted.Of the 8 lambs fed milk from MVV/scrapie-infected sheep, 1 was sacrificed early and 4 developed clinical signs of scrapie at 23 to 28 months p.i. (Table (Table1).1). The 3 remaining MVV/scrapie-exposed lambs and all control lambs were sacrificed between 28 and 29 months p.i. Both lambs orally inoculated with scrapie brain had PrPSc deposits detectable in the brain. The lamb from the MVV/scrapie group that was sacrificed early (12 months p.i.) had developed an intercurrent illness and had no biochemical or histologic evidence of scrapie infection. However, 6 of the 7 (86%) remaining lambs exposed to milk from the MVV/scrapie-infected dams had detectable PrPSc in the brain and lymphoid tissues (Fig. (Fig.2),2), indicating that infection from prion-laden milk was dependent on mammary gland inflammation. No lambs fed milk from the scrapie-only infected dams had detectable PrPSc. We considered that horizontal transmission of prions could have occurred within the MVV/scrapie-exposed lambs; however, Sardinian strains of sheep scrapie are not efficiently transmitted in ARQ/ARQ Sarda sheep, with a maximum recorded prevalence of 41% and an average prevalence of 13% (7).Open in a separate windowFIG. 2.Lambs developed prion infection through suckling milk from scrapie-infected sheep with mastitis. Brainstem and tonsil from lambs ingesting milk from MVV/scrapie- or scrapie-infected sheep were immunostained for PrP (A) or proteinase K digested (PK) and examined by Western blotting (B). The results show that only the lambs suckling the milk derived from MVV/scrapie-infected sheep accumulated PrPSc. The sheep identification number is indicated for each lane. scr+, scrapie-positive control; scr−, scrapie-negative control. Scale bars = 100 μm.Previous studies have found that the cellular fraction of milk harbors the most infectivity (4), and the higher leukocyte count in milk that occurs with mastitis could conceivably have increased the infectious prion titers in milk. Our studies in ARQ/ARQ sheep suggest that mammary gland inflammation is necessary for prion transmission through milk, although it remains possible that large milk volumes from sheep without mastitis would transmit prions to nursing lambs. Indeed, milk from VRQ/VRQ sheep without clinical mastitis was previously shown to transmit prion infection to the lambs, as evidenced by PrPSc deposits in lymphoid tissue biopsy specimens (3).Taken together, these findings demonstrate that the ingestion of as little as 1 to 2 liters of milk from sheep with scrapie and lymphofollicular mastitis can cause prion infection in ARQ/ARQ lambs at an attack rate of 86%. These data show that a common lentivirus can induce an inflammatory setting highly conducive for prion propagation and secretion in milk, although a role for the virus in transporting prions into the milk or stimulating PrPSc release from infected cells (6) cannot be excluded. Considering that MVV and other lentiviruses are endemic in sheep and goat populations worldwide, the possibility that lentiviruses have enabled prion transmission through milk and, ultimately, the propagation of scrapie through some flocks should be considered. Together with two other recent reports on infectious prions in sheep milk (3, 4), these studies indicate a risk of prion spread to sheep and, potentially, other animals through dietary exposure to sheep milk or milk products. World milk production contributes up to 13% of the protein supply for humans; thus, studies to determine the extent of infectious prions entering our global food supply would be worthwhile and important for accurate risk assessment. 相似文献
TABLE 1.
Genotype, breed, and PrPSc detection in lambs fed milk from MVV/scrapie- or scrapie-infected sheepLamb (dimorphisma) | Milk source infected with: | Amt of milk ingested (liters) | Breed | Clinical signs present | PrPSc detected by WB/IHC in: | Time point postinoculation (mo) | |
---|---|---|---|---|---|---|---|
Brain | Tonsil | ||||||
951 | MVV/Scrapie | 1.2 | Cheviot | No | −/− | −/− | 12 |
326 (127G/V) | MVV/Scrapie | 1.9 | Sarda | No | −/− | −/− | 28 |
328 (127G/V) | MVV/Scrapie | 1.8 | Sarda | Yes | +/+ | +/+ | 28 |
327 | MVV/Scrapie | 1.4 | Sarda | Yes | +/+ | +/+ | 25 |
847 | MVV/Scrapie | 1.3 | Cheviot | Yes | +/+ | +/+ | 23 |
329 | MVV/Scrapie | 2.1 | Sarda | Yes | +/+ | +/+ | 25 |
843 (141F/L) | MVV/Scrapie | 1.3 | Cheviot | No | +/+ | +/+ | 28 |
849 (141F/L) | MVV/Scrapie | 1.8 | Cheviot | No | +/+ | +/+ | 29 |
953 (141F/L) | Scrapie | 1.5 | Cheviot | No | −/− | −/− | 28 |
956 (141F/L) | Scrapie | 1.7 | Cheviot | No | −/− | −/− | 28 |
957 (141F/L) | Scrapie | 1.4 | Cheviot | No | −/− | −/− | 28 |
178.
179.
Deokiee Chon Kenneth C Beck Brett A Simon Hidenori Shikata Osama I Saba Eric A Hoffman 《Journal of applied physiology》2007,102(4):1535-1544
Xenon computed tomography (Xe-CT) is used to estimate regional ventilation by measuring regional attenuation changes over multiple breaths while rebreathing a constant Xe concentration ([Xe]). Xe-CT has potential human applications, although anesthetic properties limit [Xe] to 相似文献
180.
Using data from Bangladesh, this paper examines how the birth order of a child influences parental decisions to place children in one of four activities: 'study only', 'study and work', 'neither work nor study' and 'work only'. The results of the multinomial logit model show that being a first-born child increases the probability of work as the prime activity, or at least a combination of school and work, rather than schooling only. The results confirm that later-born children are more likely to be in school than their earlier-born counterparts. 相似文献