全文获取类型
收费全文 | 3785篇 |
免费 | 408篇 |
国内免费 | 1篇 |
出版年
2022年 | 28篇 |
2021年 | 61篇 |
2019年 | 38篇 |
2018年 | 43篇 |
2017年 | 28篇 |
2016年 | 85篇 |
2015年 | 115篇 |
2014年 | 148篇 |
2013年 | 159篇 |
2012年 | 196篇 |
2011年 | 184篇 |
2010年 | 106篇 |
2009年 | 112篇 |
2008年 | 163篇 |
2007年 | 155篇 |
2006年 | 138篇 |
2005年 | 120篇 |
2004年 | 137篇 |
2003年 | 129篇 |
2002年 | 126篇 |
2001年 | 98篇 |
2000年 | 100篇 |
1999年 | 77篇 |
1998年 | 45篇 |
1997年 | 28篇 |
1996年 | 28篇 |
1995年 | 36篇 |
1994年 | 33篇 |
1993年 | 46篇 |
1992年 | 80篇 |
1991年 | 71篇 |
1990年 | 68篇 |
1989年 | 67篇 |
1988年 | 67篇 |
1987年 | 62篇 |
1986年 | 43篇 |
1985年 | 50篇 |
1984年 | 68篇 |
1983年 | 49篇 |
1982年 | 38篇 |
1981年 | 35篇 |
1980年 | 45篇 |
1979年 | 45篇 |
1978年 | 46篇 |
1977年 | 42篇 |
1976年 | 54篇 |
1975年 | 44篇 |
1974年 | 39篇 |
1973年 | 46篇 |
1972年 | 30篇 |
排序方式: 共有4194条查询结果,搜索用时 31 毫秒
11.
The 230-kDa gamete surface protein of Plasmodium falciparum is also a target for transmission-blocking antibodies 总被引:14,自引:0,他引:14
I A Quakyi R Carter J Rener N Kumar M F Good L H Miller 《Journal of immunology (Baltimore, Md. : 1950)》1987,139(12):4213-4217
Immunization with extracellular sexual stages of the malaria parasites can induce the production of antibodies which block the development of the parasites in the midgut of a mosquito after a blood meal. We have generated a number of monoclonal antibodies against gametes and zygotes of the human malaria Plasmodium falciparum. Two monoclonal antibodies (mAb) reacting with a 230-kDa gamete surface protein (mAb 1B3 and 2B4 both isotype IgG2a) were found to block transmission of P. falciparum to mosquitoes. Blocking was complement dependent and this was verified in vitro by the rapid lysis of newly formed gametes and zygotes in the presence of the mAb and active complement. Both mAb reacted by immunofluorescence with the surface of gametes and zygotes from isolates of P. falciparum from various geographical areas. Each mAb immunoprecipitated a 230-kDa protein from 125I-labeled surface proteins of newly formed gametes and zygotes and immunoblotted a protein doublet of about molecular mass 260 and 230 kDa from gametocytes and gametes of P. falciparum. Only the 230-kDa protein is expressed on the surface of newly formed macrogametes and zygotes. The 230-kDa gamete surface protein forms a molecular complex with two proteins of 48 and 45 kDa. The 48- and 45-kDa gamete surface proteins have previously been shown to be targets of mAb which block infectivity of P. falciparum to mosquitoes. The present study now demonstrates that antibodies against the 230-kDa gamete surface protein block transmission of P. falciparum to mosquitoes. The 230-kDa gamete protein is thus a potential candidate for a gamete vaccine. 相似文献
12.
O. Carter Snead III 《Journal of neurochemistry》1987,48(1):196-201
The presence of gamma-hydroxybutyric acid (GHB) in synaptosome-enriched fractions of rat brain was ascertained using a GLC technique. The stability of GHB in synaptosomes was evaluated by addition of various gamma-aminobutyric acid (GABA) transaminase (GABA-T) inhibitors, GHB, or ethosuximide to the homogenizing medium. Furthermore, changes in whole brain GHB levels were compared with those in the synaptosomal fraction in animals treated with GABA-T inhibitors, GABA, or ethosuximide. GHB was present in synaptosome-enriched fractions in concentrations ranging from 40 to 70 pmol/mg of protein. There was no evidence for redistribution, leakage, or metabolism of GHB during the preparation of synaptosomes. The elevations of whole brain GHB level associated with GABA-T or ethosuximide treatment were reflected by a parallel increase in synaptosomal GHB content. These data add to the growing evidence that GHB may have neurotransmitter or neuromodulator function. 相似文献
13.
Small rodents and other mammals associated with mountain meadows as reservoirs of Giardia spp. and Campylobacter spp. 总被引:1,自引:0,他引:1
下载免费PDF全文
![点击此处可从《Applied microbiology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
R E Pacha G W Clark E A Williams A M Carter J J Scheffelmaier P Debusschere 《Applied microbiology》1987,53(7):1574-1579
Sixty-five percent (469 of 722) of the fecal samples collected from small rodents in the central Washington Cascade mountains were positive for Giardia spp. Trapping studies showed that microtines of the genus Microtus were heavily infected with the parasite. Morphologically the cysts and trophozoites were of the Giardia duodenalis type. Small-rodent populations appear to maintain their infection throughout the year. Our data suggest that there is no difference in the percentage of positive animals in areas receiving a lot of human use as opposed to animals in those areas receiving very little or no human use. Giardia spp. were also found in elk and beaver fecal samples. Campylobacter spp. were recovered infrequently from the small rodents inhabiting alpine meadows. Of 551 specimens cultured, less than 1% were positive for the bacterium, and the isolates were identified as Campylobacter coli. Water voles were susceptible to a human isolate of Campylobacter jejuni and shed the bacterium for several weeks. C. jejuni was also isolated from a bear fecal sample collected from a protected watershed. Our studies indicate that microtines and possibly other small rodents inhabiting mountain meadows have a potential to act as a reservoir for both Giardia spp. and Campylobacter spp. Because these animals may carry human pathogens, they should be included in animal surveys designed to assess the health risks associated with mountain watersheds. 相似文献
14.
Seasonal occurrence of Campylobacter spp. in surface waters and their correlation with standard indicator bacteria.
下载免费PDF全文
![点击此处可从《Applied microbiology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Campylobacter jejuni, Campylobacter coli, and a Campylobacter-like organism were isolated from a number of natural water sources in central Washington, including ponds, lakes, and small mountain streams at elevations ranging from 1,460 to 5,400 feet (ca. 445 to 1,646 m) above sea level. At the two sites where extensive sampling was done, the bacteria were recovered throughout the year. Generally, the recovery rates were highest in the fall and winter months and lowest during the spring and summer months. Campylobacter density did not show significant correlation with microbiological (plate counts of fecal and total coliforms, fecal streptococci, and heterotrophic bacteria) or physical (water temperature, pH, and conductivity) parameters. 相似文献
15.
Despite their physicochemical and mechanistic differences platelet activating factor (or acetylglycerylether phosphorylcholine; AGEPC) and thrombin, both platelet stimulatory agents, induce phosphoinositide turnover in platelets. We therefore investigated the stimulation of the phosphoinositide phosphodiesterase by these agents and questioned whether they evoked hydrolysis of the same or different pools of phosphoinositides. [3H]Inositol-labelled rabbit platelets were challenged with thrombin and/or AGEPC under a variety of protocols, and the phospholipase C mediated production of radioactive inositol monophosphate (IP); inositol bisphosphate (IP2) and inositol trisphosphate (IP3) was used as the parameter. AGEPC (1 X 10(-9) M) caused a transient maximum (5 to 6-fold) increase in [3H]IP3 at 5 s followed by a decrease. Thrombin (2 U/ml) elicited an increase in [3H]IP3 at a much slower rate than AGEPC; 2 fold at 5 s, 5 fold at 30 s and a maximum 6 to 8-fold at 2-5 min. Compared to AGEPC, thrombin stimulated generation of [3H]IP2 and [3H]IP were severalfold higher. When thrombin and AGEPC were added together to platelets there was no evidence for an additive increase in inositol polyphosphate levels except at earlier time points where increases were submaximal. When AGEPC was added at various time intervals after thrombin pretreatment, no additional increases in [3H]IP3 were observed over that maximally seen with thrombin or AGEPC alone. In another set of experiments, submaximal increases (about 1/4 and 1/2 of maximum) in [3H]IP3 were achieved by using selected concentrations of thrombin (0.1 U and 0.3 U, respectively) and then AGEPC (1 X 10(-9) M) was added for 5 s. Once again the increase in [3H]IP3 was close to the maximal level seen with thrombin or AGEPC individually. It is concluded that thrombin and AGEPC differentially activated phosphoinositide phosphodiesterase (phospholipase C) in rabbit platelets and that the stimulation of the phospholipase C by these two stimuli causes IP3 production via hydrolysis of a common pool of phosphatidylinositol 4,5-bisphosphate. 相似文献
16.
The fungicide methyl 2-benzimidazole carbamate causes infertility in male Sprague-Dawley rats 总被引:2,自引:0,他引:2
A serial breeding technique was used to evaluate the fertility of male Sprague-Dawley rats after exposure to the fungicide carbendazim (methyl 2-benzimidazole carbamate). Proven-fertile male rats (90 days old) received 10 daily doses of corn oil or carbendazim (400 mg/kg/day) peroral. Each male was bred with a new female each week; breeding began on the third day of treatment and continued for 32 wk after the last day of chemical exposure. Twelve days after each breeding period, the females were killed, their uteri were examined for resorptions, and the number of dead and viable fetuses was determined. All males were killed 35 wk post exposure, and testicular tissue was prepared for histopathological examination by vascular perfusion. Fertility (percent fertile as indicated by pregnant females) of males in the carbendazim-treated group was depressed the first post-exposure week; 10 of the 24 treated males failed to produce a pregnant female as compared with no failures in the control group. By the fifth post-exposure week, 16 of the 24 carbendazim-treated males were infertile. Of these 16 males, 4 recovered fertility after a failure to produce a pregnant female for 5-11 consecutive breeding periods. However, 12 of the males did not recover fertility during the remainder of the 32-wk post-exposure period. Histological examinations of testicular sections 245 days post exposure revealed that exposure to carbendazim caused severe seminiferous tubular atrophy (greater than 85% of tubules were atrophic) in those carbendazim-treated males that failed to recover fertility.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
17.
Exclusion of linkage of loci on chromosome 19 with multiple endocrine neoplasia, type 2 总被引:2,自引:0,他引:2
C Carter D F Easton C G Mathew G Welander H Telenius M Telenius-Berg B A Ponder 《Cytogenetics and cell genetics》1987,45(1):33-37
Linkage between seven loci on chromosome 19 and multiple endocrine neoplasia type 2a (MEN2A) was examined in a single large Swedish pedigree. A total of 50 cM was excluded from the male genetic map by pairwise analysis and an estimated 63 cM by multipoint analysis. Using existing data on the likelihood of different marker-marker distances and taking into account current exclusions on other chromosomes, the probability that the gene for MEN2A segregating in this pedigree could still be located on chromosome 19 is approximately 0.28%. 相似文献
18.
Effects of the wasp venom peptide, mastoparan, on a phosphoinositide-specific phospholipase C purified from rabbit brain membranes 总被引:3,自引:0,他引:3
The wasp venom peptide, mastoparan (Ile-Asn-Leu-Lys-Ala-Leu-Ala-Ala-Leu-Ala-Lys-Lys-Ile-LeuNH2), activated phosphatidylinositol 4,5-bisphosphate (PIP2) hydrolysis as catalyzed by a phosphoinositide-specific phospholipase C (PLC-Im) purified from rabbit brain membranes. This activation was found when the molar ratio of mastoparan to PIP2 was less than 1 and when the concentration of PIP2 exceeded 10 microM. PIP2 breakdown was inhibited at both high and low substrate concentrations if the molar ratio of mastoparan to PIP2 was greater than 1. The stimulatory effect of mastoparan correlated with its ability to restrict aggregation of PIP2 into higher order structures (liposomes or mixed deoxycholate/phospholipid micelles) as the concentration of PIP2 was increased to 10 microM or greater. Mastoparan stimulation of PIP2 breakdown required the presence of a higher calcium concentration than was necessary for detection of enzyme activity. Both the stimulatory and inhibitory effects of mastoparan on PIP2 hydrolysis were lost if 2.5 mM deoxycholate was present in the assays. Hydrolysis of phosphatidylinositol (PI) by PLC-Im was inhibited at all concentrations of mastoparan tested. These results show that both PIP2 and PI are suitable substrates for PLC-Im, depending on the physical characteristics of their aggregates in aqueous suspension. An amphiphilic alpha-helix-forming peptide such as mastoparan may modulate phospholipase C activity due to the peptide's interaction with phospholipid substrates. 相似文献
19.
Cell migration on fibronectin (FN)-coated substrata was studied using 10 cell lines, of which only 2 showed clear enhancement and 1 showed marginal enhancement of cell migration. The migration of the other 7 cell lines was not affected on FN-coated substrata, although they all showed FN-dependent cell adhesion. The migration-enhancing activity of FN was found in the fragment including the cell-adhesion and Hep-2 domains, but not other domains (Hep-1/Fib-1, Gel, Fib-2). No difference in the migration-enhancing effect was seen among FNs from plasma, fibroblasts, or transformed cells. FN-dependent cell migration was inhibited by polyclonal antibodies directed to the C-terminal half region including the cell binding domain, but not by antibodies directed to five other domains. Since these results indicated that FN-mediated cell migration could be controlled by the cell-adhesion domain of FN and its receptor, studies were then focused on the effect of antibodies directed to receptors for FN and collagen, and on the effect of tetrapeptide sequences recognized by these receptors. It was found that (i) cell migration on FN-coated surfaces was specifically inhibited by anti-FN receptor antibody P1F8 but not by anticollagen receptor antibody P1H5; (ii) the migration was strongly inhibited by Arg-Gly-Asp-Ser but not by other oligopeptide sequences. However, the majority of those cell lines not susceptible to FN-dependent cell migration were characterized by having FN receptors and the ability to adhere on FN-coated matrix. Based on these findings, it was concluded that FN-dependent cell migration shares the same recognition mechanism as FN-dependent cell adhesion, but that the majority of cell lines not exhibiting FN-dependent migration still show FN-dependent cell adhesion and express the FN receptor (integrin); i.e., cell migration and adhesion involve the same receptor and the same FN loci, but migration is controlled by still-unidentified cellular factors which determine the susceptibility of the cell to the dynamic function of the FN receptor (integrin) unit. 相似文献
20.
J M Hall P J Zuppan L A Anderson B Huey C Carter M C King 《American journal of human genetics》1989,44(4):577-584
The role of oncogenes in breast tumorigenesis is unclear. Alterations and/or amplification of several oncogene sequences have been observed in primary human breast tumors, in breast tumor cell lines, and in mammary tumors in model systems. In principle, such alterations could be sites of primary lesions for human breast cancer, causes of tumor progression or metastasis, or simply secondary lesions of highly aberrant tumor genomes. The present study tested genetic linkage of breast cancer susceptibility to nine oncogenes in 12 extended families including 87 affected individuals. Lod scores for close linkage of each candidate sequence to breast cancer were -19.6 for HRAS, -12.3 for KRAS2, -1.0 for NRAS, -6.0 for MYC, -6.1 for MYB, -8.2 for ERBA2, -7.9 for INT2, and -5.1 for RAF1. Regions of chromosome 11p associated with tumor homozygosity and the region of 3p carrying the gene for Von Hippel-Lindau disease could also be excluded from linkage to human breast cancer. The 5-kb allele of the MOS oncogene, previously proposed to be associated with breast cancer, was absent in these families, suggesting that polymorphism at this locus is not associated with inherited susceptibility. These results strongly suggest that oncogenes are not the sites of primary alterations leading to breast cancer. On the other hand, alterations in one or more of these sequences may be associated with tumor progression. 相似文献