全文获取类型
收费全文 | 12324篇 |
免费 | 816篇 |
国内免费 | 592篇 |
专业分类
13732篇 |
出版年
2024年 | 52篇 |
2023年 | 337篇 |
2022年 | 421篇 |
2021年 | 504篇 |
2020年 | 444篇 |
2019年 | 465篇 |
2018年 | 457篇 |
2017年 | 296篇 |
2016年 | 330篇 |
2015年 | 449篇 |
2014年 | 651篇 |
2013年 | 793篇 |
2012年 | 460篇 |
2011年 | 672篇 |
2010年 | 523篇 |
2009年 | 657篇 |
2008年 | 608篇 |
2007年 | 615篇 |
2006年 | 565篇 |
2005年 | 540篇 |
2004年 | 446篇 |
2003年 | 340篇 |
2002年 | 333篇 |
2001年 | 251篇 |
2000年 | 195篇 |
1999年 | 204篇 |
1998年 | 184篇 |
1997年 | 152篇 |
1996年 | 136篇 |
1995年 | 130篇 |
1994年 | 148篇 |
1993年 | 126篇 |
1992年 | 112篇 |
1991年 | 97篇 |
1990年 | 81篇 |
1989年 | 90篇 |
1988年 | 66篇 |
1987年 | 65篇 |
1986年 | 56篇 |
1985年 | 67篇 |
1984年 | 127篇 |
1983年 | 91篇 |
1982年 | 92篇 |
1981年 | 76篇 |
1980年 | 63篇 |
1979年 | 42篇 |
1978年 | 28篇 |
1977年 | 25篇 |
1976年 | 17篇 |
1975年 | 17篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
291.
电穿孔介导质粒DNA肿瘤内转移抑制恶性肿瘤生长与转移 总被引:3,自引:0,他引:3
利用携带绿色荧光蛋白(green fluorescent protein, GFP)编码基因的表达质粒,测试电穿孔方法介导目的基因活体组织内转移的效率并优化电击参数.在此基础上采用电穿孔技术直接将编码白介素12(IL-12)、白介素2(IL-2)、粒单细胞克隆刺激因子(GM-CSF)等免疫调节因子或反义血管内皮细胞生长因子121(VEGF121)、可溶性血管内皮细胞膜受体(sFlk-1及ExTek)等血管生成抑制因子表达质粒转移至肿瘤局部.实验结果表明电穿孔介导GFP表达质粒肌肉内转移的效率较高,GFP可在肌细胞内持续高水平表达3周以上,而在肿瘤细胞内只能表达4~6 d,但高电压短脉冲电击组肿瘤内GFP阳性细胞数比低电压长脉冲组高2.68倍.多次电击介导IL-12表达质粒转移至肿瘤组织内,可有效地抑制小鼠膀胱癌BTT-gfp、人乳腺癌MCF-7及肝癌SMMC 7721-gfp的生长.MCF-7对血管生成抑制因子基因转移治疗较敏感,单独应用反义VEGF121、sFlk-1或ExTek即显示明确的治疗效果.SMMC 7721-gfp单独应用sFlk-1有效.小鼠膀胱癌对单独应用反义VEGF121、sFlk-1或ExTek治疗效果不理想,但联合应用sFlk-1和ExTek仍然可以有效地抑制肿瘤生长与转移,甚至使肿瘤缩小或消失.提示电穿孔技术是一项高效、安全、经济的体内基因转移方法. 相似文献
292.
Summary We have studied the course of the operculum line in the larval hypoderm of several bithorax complex mutants of Drosophila melanogaster. The bifurcation of the line, a characteristic of the first abdominal segment in wild-type (A1), can also appear in the metathoracic (T3) and other abdominal segments (A2, A3) depending on mutations within the bithorax complex. Therefore, we concluded that the course of the operculum line and thus the shape of the operculum is not determined by a suprasegmental gradient of positional information but by the functional state of the genes of the bithorax complex in each metamere. The dorsal and ventral branches of the operculum line react differently, the dorsal branch being more sensitive to the effect of loss of function mutations (bxd, iab-2
k), the ventral branch more affected by gain of function mutations (Hab). In some cases the effects of the mutations on the operculum line differed from those in the adult, suggesting a difference in sensitivity of larval hypodermal cells and histoblast cells to the functional gene products of the bithorax complex. 相似文献
293.
294.
Wilbur AK Engel GA Rompis A A Putra IG Lee BP Aggimarangsee N Chalise M Shaw E Oh G Schillaci MA Jones-Engel L 《American journal of primatology》2012,74(7):676-686
Although the Mycobacterium tuberculosis complex (MTBC) infects a third of all humans, little is known regarding the prevalence of mycobacterial infection in nonhuman primates (NHP). For more than a century, tuberculosis has been regarded as a serious infectious threat to NHP species. Advances in the detection of MTBC open new possibilities for investigating the effects of this poorly understood pathogen in diverse populations of NHP. Here, we report results of a cross-sectional study using well-described molecular methods to detect a nucleic acid sequence (IS6110) unique to the MTBC. Sample collection was focused on the oral cavity, the presumed route of transmission of MTBC. Buccal swabs were collected from 263 macaques representing 11 species in four Asian countries and Gibraltar. Contexts of contact with humans included free ranging, pets, performing monkeys, zoos, and monkey temples. Following DNA isolation from buccal swabs, the polymerase chain reaction (PCR) amplified IS6110 from 84 (31.9%) of the macaques. In general, prevalence of MTBC DNA was higher among NHP in countries where the World Health Organization reports higher prevalence of humans infected with MTBC. This is the first demonstration of MTBC DNA in the mouths of macaques. Further research is needed to establish the significance of this finding at both the individual and population levels. PCR of buccal samples holds promise as a method to elucidate the mycobacterial landscape among NHP, particularly macaques that thrive in areas of high human MTBC prevalence. 相似文献
295.
296.
Ross A. Robinson Samuel C. Griffiths Lieke L. van de Haar Tomas Malinauskas Eljo Y. van Battum Pavol Zelina Rebekka A. Schwab Dimple Karia Lina Malinauskaite Sara Brignani Marleen H. van den Munkhof Özge Düdükcü Anna A. De Ruiter Dianne M.A. Van den Heuvel Benjamin Bishop Jonathan Elegheert A. Radu Aricescu R. Jeroen Pasterkamp Christian Siebold 《Cell》2021,184(8):2103-2120.e31
297.
We investigated the relationship between host defense and specialization by parasites in comparative analyses of bird fleas and T-cell mediated immune response of their avian hosts, showing that fleas with few main host species exploited hosts with weak or strong immune defenses, whereas flea species that parasitized a large number of host species only exploited hosts with weak immune responses. Hosts with strong immune responses were exploited by a larger number of flea species than hosts with weak responses. A path analysis model with an effect of T-cell response on the number of host species, or a model with host coloniality directly affecting host T-cell response, which in turn affected the number of host species used by fleas, best explained the data. Therefore, parasite specialization may have evolved in response to strong host defenses. 相似文献
298.
Genes of the major histocompatibility complex (MHC) have a crucial role in the immune response of vertebrates, alter the individual odour and are involved in shaping mating preferences. Pathogen-mediated selection, sexual selection and maternal-fetal interactions have been proposed as the main drivers of frequently observed high levels of polymorphism in functionally important parts of the MHC. Bats constitute the second largest mammalian order and have recently emerged as important vectors of infectious diseases. In addition, Chiroptera are interesting study subjects in evolutionary ecology in the context of olfactory communication, mate choice and associated fitness benefits. Thus, it is surprising that they belong to the least studied mammalian taxa in terms of their MHC diversity. In this study, we investigated the variability in the functionally important MHC class II gene DRB, evidence for selection and population structure in the group-living lesser bulldog bat, Noctilio albiventris, in Panama. We found a single expressed, polymorphic Noal-DRB gene. The substitution pattern of the nucleotide sequences of the 18 detected alleles provided evidence for positive selection acting above the evolutionary history of the species in shaping MHC diversity. Roosting colonies were not genetically differentiated but females showed lower levels of heterozygosity than males, which might be a sign that the sexes differ in the selection pressures acting on the MHC. This study provides the prerequisites for further investigations of the role of the individual MHC constitution in parasite resistance, olfactory communication and mate choice in N. albiventris and other bats. 相似文献
299.
A. A. Kolobov N. I. Kolodkin Yu. A. Zolotarev C. Tuthill E. V. Navolotskaya 《Russian Journal of Bioorganic Chemistry》2008,34(1):37-42
The tritium-labeled dipeptide bestim (γ-D-Glu-L-Trp) with a specific activity of 45 Ci/mmol was obtained by high-temperature solid-state catalytic isotope exchange. It was found that [3H]bestim binds with a high affinity to murine peritoneal macrophages (K d 2.1 ± 0.1 nM) and thymocytes (K d 3.1 ± 0.2 nM), as well as with plasma membranes isolated from these cells (K d 18.6 ± 0.2 and 16.7 ± 0.3 nM, respectively). The specific binding of [3H]bestim to macrophages and thymocytes was inhibited by the unlabeled dipeptide thymogen (L-Glu-L-Trp) (K i 0.9 ± 0.1 and 1.1 ± 0.1 nM, respectively). After treatment with trypsin, macrophages and thymocytes lost the ability to bind [3H]bestim. Bestim in the concentration range of 10?10 to 10?6 M reduced the adenylate cyclase activity in the membranes of murine macrophages and thymocytes. 相似文献
300.
The orientation of pigments and pigment-protein complexes of the green photosynthetic bacterium Prosthecochloris aestuarii was studied by measurement of linear dichroism spectra at 295 and 100 K. Orientation of intact cells and membrane vesicles (Complex I) was obtained by drying on a glass plate. The photochemically active pigment-protein complexes (photosystem-protein complex and reaction center pigment-protein complex) and the antenna bacteriochlorophyll a protein were oriented by pressing a polyacrylamide gel. The data indicate that the near-infrared transitions (Qy) of bacteriochlorophyll c and most bacteriochlorophyll a molecules have a relatively parallel orientation to the membrane, whereas the Qy transitions of the bacteriochlorophyll a in the antenna protein are oriented predominantly perpendicularly to the membrane. Carotenoids and the Qx transitions (590–620 nm) of bacteriochlorophyll a, not belonging to the bacteriochlorophyll a protein, have a relatively perpendicular orientation to the membrane. The absorption and linear dichroism spectra indicate the existence of different pools of bacteriochlorophyll c in the chlorosomes and of carotenoid and bacteriopheophytin c in the cell membrane. The results suggest that the photosystem-protein and reaction center pigment-protein complexes are oriented with their short axes approximately perpendicular to the plane of the membrane. The symmetry axis of the bacteriochlorophyll a protein has an approximately perpendicular orientation. 相似文献