全文获取类型
收费全文 | 4812篇 |
免费 | 321篇 |
国内免费 | 5篇 |
专业分类
5138篇 |
出版年
2023年 | 31篇 |
2022年 | 47篇 |
2021年 | 90篇 |
2020年 | 87篇 |
2019年 | 53篇 |
2018年 | 160篇 |
2017年 | 138篇 |
2016年 | 190篇 |
2015年 | 231篇 |
2014年 | 230篇 |
2013年 | 344篇 |
2012年 | 351篇 |
2011年 | 349篇 |
2010年 | 220篇 |
2009年 | 169篇 |
2008年 | 272篇 |
2007年 | 267篇 |
2006年 | 229篇 |
2005年 | 218篇 |
2004年 | 209篇 |
2003年 | 218篇 |
2002年 | 161篇 |
2001年 | 77篇 |
2000年 | 77篇 |
1999年 | 60篇 |
1998年 | 42篇 |
1997年 | 30篇 |
1996年 | 26篇 |
1995年 | 31篇 |
1994年 | 32篇 |
1993年 | 16篇 |
1992年 | 30篇 |
1991年 | 26篇 |
1990年 | 35篇 |
1989年 | 32篇 |
1988年 | 21篇 |
1987年 | 17篇 |
1986年 | 20篇 |
1985年 | 18篇 |
1984年 | 41篇 |
1983年 | 18篇 |
1982年 | 19篇 |
1981年 | 27篇 |
1980年 | 19篇 |
1979年 | 16篇 |
1978年 | 11篇 |
1977年 | 11篇 |
1975年 | 10篇 |
1972年 | 10篇 |
1971年 | 10篇 |
排序方式: 共有5138条查询结果,搜索用时 0 毫秒
111.
Costa L Brissos V Lemos F Ribeiro FR Cabral JM 《Bioprocess and biosystems engineering》2008,31(4):323-327
The activity of various lipases was compared, in both free and immobilized forms, using the kinetics of the hydrolysis reaction of p-nitrophenyl butyrate, which was followed with in situ UV/Vis diode array spectrophotometry. Several enzymes were used to catalyze the reaction, namely Candida antarctica lipase B and Fusarium solani pisi cutinase wildtype and three single-mutation variants. The enzymes were tested in three different forms: free, immobilized as cross-linked aggregates and supported on zeolite NaY. A simple kinetic model was used to allow a quantitative comparison of the behavior of the different catalysts. It was concluded that although immobilization reduces the activity of the enzyme, the zeolite offers a much higher specific activity when compared to the cross-linked aggregates, thus supplying a heterogeneous catalyst with promising catalytic properties. 相似文献
112.
Anand Kumar Seema Singh Satyajit Pradhan Ram C Shukla Mumtaz A Ansari Tej B Singh Rohit Shyam Saroj Gupta 《World journal of surgical oncology》2007,5(1):1-6
Background
Von Hippel-Lindau (VHL) disease is an autosomal dominant inherited disease. It is relatively recent that type 2C was identified as a separate group solely presenting with pheochromocytomas. As an illustration, an interesting case is presented of a pregnant woman with refractory hypertension. It proved to be the first manifestation of bilateral pheochromocytomas. The family history may indicate the diagnosis, but only identification of a germ line mutation in the DNA of a patient will confirm carriership.Case presentation
A 27 year pregnant patient with intra uterine growth retardation presented with hypertension and pre-eclampsia. Magnetic resonance imaging revealed bilateral adrenal pheochromocytoma. She underwent laparoscopic adrenelectomy and a missense mutation (Gly93Ser) in exon 1 of the VHL gene on chromosome 3 (p25 - p26) was shown in the patient, her father and her daughter confirming the diagnosis of VHL.Conclusion
In almost all VHL families molecular genetic analysis of DNA will demonstrate an inherited mutation. Because of the involvement in several organs, periodic clinical evaluation should take place in a well coordinated, multidisciplinary setting. VHL disease can be classified into several subtypes. VHL type 2C patients present with pheochromocytomas without evidence of haemangioblastomas in the central nervous system and/or retina and a low risk of renal cell carcinoma. Therefore, in such families, periodic clinical screening can be focussed on pheochromocytomas. 相似文献113.
The effects of vetrabutin chlorhydrate and oxytocin on stillbirth rate and asphyxia in swine 总被引:1,自引:0,他引:1
Mota-Rojas D Rosales AM Trujillo ME Orozco H Ramírez R Alonso-Spilsbury M 《Theriogenology》2005,64(9):1889-1897
Oxytocin and vetrabutin chlorhydrate (VC) are used to reduce the duration of farrowing in swine. The objective of the present study was to evaluate the use of these products on intra-partum stillbirth (IPS) rate and asphyxia. At the onset of parturition, sows (n=180) were allocated to receive 2 mL of saline (control group), oxytocin (40 IU i.m.) or 100mg of VC per 60 kg of body weight, with all treatments given i.m. Oytocin-treated sows had a higher number of IPS than the VC and Control groups (means, 1.2, 0.8 and 0.6, respectively; P<0.001), and the highest percentage of ruptured umbilical cords (76.0, 9.4 and 37.5%; P<0.003). There were differences among groups for duration of farrowing (means, 163.0, 211.2 and 306.9 min in the oxytocin, VC and control groups; P<0.001), interval between piglets (13.9, 19.2 and 28.1 min; P<0.001), and in IPS, the incidence of ruptured umbilical cords was 76.0, 9.4 and 37.5% (P<0.003) and absence of a fetal heartbeat was 53.3, 16.9 and 12.5% (P<0.05). Although oxytocin decreased both duration of farrowing and interval between piglets by approximately 50% relative to control sows, it resulted in a significantly higher rate of IPS, in association with a much higher incidence of ruptured umbilical cord and absence of a fetal heartbeat. Treatment with VC reduced farrowing duration by approximately 1.5h, with an IPS rate that was not significantly different from controls but significantly lower than that of oxytocin-treated sows. 相似文献
114.
115.
Singh RP Kashiwamura S Rao P Okamura H Mukherjee A Chauhan VS 《Journal of immunology (Baltimore, Md. : 1950)》2002,168(9):4674-4681
A possible protective role of IL-18 in host defense against blood-stage murine malarial infection was studied in BALB/c mice using a nonlethal strain, Plasmodium yoelii 265, and a lethal strain, Plasmodium berghei ANKA. Infection induced an increase in mRNA expression of IL-18, IL-12p40, IFN-gamma, and TNF-alpha in the case of P. yoelii 265 and an increase of IL-18, IL-12p40, and IFN-gamma in the case of P. berghei ANKA. The timing of mRNA expression of IL-18 in both cases was consistent with a role in the induction of IFN-gamma protein expression. Histological examination of spleen and liver tissues from infected controls treated with PBS showed poor cellular inflammatory reaction, massive necrosis, a large number of infected parasitized RBCs, and severe deposition of hemozoin pigment. In contrast, IL-18-treated infected mice showed massive infiltration of inflammatory cells consisting of mononuclear cells and Kupffer cells, decreased necrosis, and decreased deposition of the pigment hemozoin. Treatment with rIL-18 increased serum IFN-gamma levels in mice infected with both parasites, delayed onset of parasitemia, conferred a protective effect, and thus increased survival rate of infected mice. Administration of neutralizing anti-IL-18 Ab exacerbated infection, impaired host resistance and shortened the mean survival of mice infected with P. berghei ANKA. Furthermore, IL-18 knockout mice were more susceptible to P. berghei ANKA than were wild-type C57BL/6 mice. These data suggest that IL-18 plays a protective role in host defense by enhancing IFN-gamma production during blood-stage infection by murine malaria. 相似文献
116.
117.
Kakajan Komurov Jen‐Te Tseng Melissa Muller Elena G Seviour Tyler J Moss Lifeng Yang Deepak Nagrath Prahlad T Ram 《Molecular systems biology》2012,8(1)
Dynamic interactions between intracellular networks regulate cellular homeostasis and responses to perturbations. Targeted therapy is aimed at perturbing oncogene addiction pathways in cancer, however, development of acquired resistance to these drugs is a significant clinical problem. A network‐based computational analysis of global gene expression data from matched sensitive and acquired drug‐resistant cells to lapatinib, an EGFR/ErbB2 inhibitor, revealed an increased expression of the glucose deprivation response network, including glucagon signaling, glucose uptake, gluconeogenesis and unfolded protein response in the resistant cells. Importantly, the glucose deprivation response markers correlated significantly with high clinical relapse rates in ErbB2‐positive breast cancer patients. Further, forcing drug‐sensitive cells into glucose deprivation rendered them more resistant to lapatinib. Using a chemical genomics bioinformatics mining of the CMAP database, we identified drugs that specifically target the glucose deprivation response networks to overcome the resistant phenotype and reduced survival of resistant cells. This study implicates the chronic activation of cellular compensatory networks in response to targeted therapy and suggests novel combinations targeting signaling and metabolic networks in tumors with acquired resistance. 相似文献
118.
Clotfelter ED Pedersen AB Cranford JA Ram N Snajdr EA Nolan V Ketterson ED 《Oecologia》2007,154(3):493-503
Resource pulses can have cascading effects on the dynamics of multiple trophic levels. Acorn mast is a pulsed resource in
oak-dominated forests that has significant direct effects on acorn predators and indirect effects on their predators, prey,
and pathogens. We evaluated changes in acorn mast, rodent abundance, raptor abundance, and reproductive success of a ground-nesting
songbird over a 24-year period (1980–2004) in the southern Appalachian Mountains in an effort to determine the relationships
among the four trophic levels. In particular, we examined the following: acorn mast from red oaks (Quercus rubra) and white oaks (Q. alba), abundance of white-footed mice (Peromyscus leucopus) and deer mice (P. maniculatus), population estimates of seven raptor species from three feeding guilds, and nest failure and number of juveniles of dark-eyed
juncos (Junco hyemalis). Finally, we recorded seasonal temperature and precipitation to determine the effects of weather on each trophic level.
We found that weather patterns had delayed effects of up to 3 years on these trophic interactions. Variation in acorn mast,
the keystone resource in this community, was explained by weather conditions as far back as 2 years before the mast event.
Acorn mast, in turn, was a strongly positive predictor of rodent abundance the following year, whereas spring and summer temperature
and raptor abundance negatively affected rodent abundance. Dark-eyed junco nests were more likely to fail in years in which
there were more rodents and raptors. Nest failure rate was a strong predictor of the number of juvenile juncos caught at the
end of the summer. Our results improve our understanding of the complex ecological interactions in oak-dominated forests by
illustrating the importance of abiotic and biotic factors at different trophic levels.
Ethan D. Clotfelter and Amy B. Pedersen contributed equally to the writing of this paper. 相似文献
119.
Rogers MS Hurtado-Guerrero R Firbank SJ Halcrow MA Dooley DM Phillips SE Knowles PF McPherson MJ 《Biochemistry》2008,47(39):10428-10439
Galactose oxidase (GO) belongs to a class of proteins that self-catalyze assembly of their redox-active cofactors from active site amino acids. Generation of enzymatically active GO appears to require at least four sequential post-translational modifications: cleavage of a secretion signal sequence, copper-dependent cleavage of an N-terminal pro sequence, copper-dependent formation of a C228-Y272 thioether bond, and generation of the Y272 radical. The last two processes were investigated using a truncated protein (termed premat-GO) lacking the pro sequence and purified under copper-free conditions. Reactions of premat-GO with Cu(II) were investigated using optical, EPR, and resonance Raman spectroscopy, SDS-PAGE, and X-ray crystallography. Premat-GO reacted anaerobically with excess Cu(II) to efficiently form the thioether bond but not the Y272 radical. A potential C228-copper coordinated intermediate (lambda max = 406 nm) in the processing reaction, which had not yet formed the C228-Y272 cross-link, was identified from the absorption spectrum. A copper-thiolate protein complex, with copper coordinated to C228, H496, and H581, was also observed in a 3 min anaerobic soak by X-ray crystallography, whereas a 24 h soak revealed the C228-Y272 thioether bond. In solution, addition of oxygenated buffer to premat-GO preincubated with excess Cu(II) generated the Y272 radical state. On the basis of these data, a mechanism for the formation of the C228-Y272 bond and tyrosyl radical generation is proposed. The 406 nm complex is demonstrated to be a catalytically competent processing intermediate under anaerobic conditions. We propose a potential mechanism which is in common with aerobic processing by Cu(II) until the step at which the second electron acceptor is required. 相似文献
120.
The Rose Bengal Test in human brucellosis: a neglected test for the diagnosis of a neglected disease
Brucellosis is a highly contagious zoonosis affecting livestock and human beings. The human disease lacks pathognomonic symptoms and laboratory tests are essential for its diagnosis. However, most tests are difficult to implement in the areas and countries were brucellosis is endemic. Here, we compared the simple and cheap Rose Bengal Test (RBT) with serum agglutination, Coombs, competitive ELISA, Brucellacapt, lateral flow immunochromatography for IgM and IgG detection and immunoprecipitation with Brucella proteins. We tested 208 sera from patients with brucellosis proved by bacteriological isolation, 20 contacts with no brucellosis, and 1559 sera of persons with no recent contact or brucellosis symptoms. RBT was highly sensitive in acute and long evolution brucellosis cases and this related to its ability to detect IgM, IgG and IgA, to the absence of prozones, and to the agglutinating activity of blocking IgA at the pH of the test. RBT was also highly specific in the sera of persons with no contact with Brucella. No test in this study outperformed RBT, and none was fully satisfactory in distinguishing contacts from infected patients. When modified to test serum dilutions, a diagnostic titer >4 in RBT resulted in 87.4% sensitivity (infected patients) and 100% specificity (contacts). We discuss the limitations of serological tests in the diagnosis of human brucellosis, particularly in the more chronic forms, and conclude that simplicity and affordability of RBT make it close to the ideal test for small and understaffed hospitals and laboratories. 相似文献