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41.
42.
Lev G. Goldfarb Paul Brown Larisa Cervenakova D. Carleton Gajdusek 《Molecular neurobiology》1994,8(2-3):89-97
Genetic study of over 200 cases of Creutzfeldt-Jakob disease (CJD), Gerstmann-Sträussler-Scheinker disease (GSS), fatal familial insomnia (FFI), and kuru have brought a reliable body of evidence that the familial forms of CJD and all known cases of GSS and FFI are linked to germline mutations in the coding region of the PRNP gene on chromosome 20, either point substitutions or expansion of the number of repeat units. No pathogenic mutations have so far been found in sporadic or infectious forms of CJD, although there are features of genetic predisposition in iatrogenic CJD and kuru. In FFI and familial CJD, clinically and pathologically distinct syndromes that are both linked to the 178Asp→Asn substitution, phenotypic expression is dependent on a polymorphism at codon 129. Synthetic peptides homologous to several regions of PrP spontaneously form insoluble amyloid fibrils with unique morphological characteristics and polymerization tendencies. Peptides homologous to mutated regions of PrP exhibit enhanced fibrilogenic properties and, if mixed with the wild-type peptide, produce even more abundant and larger fibrous aggregates. A similar process in vivo may lead to amyloid accumulation and disease, and transmission of “baby fibrils” may induce disease in other hosts. 相似文献
43.
HBIG,无环鸟苷,干扰素联合对慢性乙型肝炎抗病毒效应观察 总被引:1,自引:0,他引:1
本文报道血清HBV复制标志阳性的慢乙肝54例,随机分为治疗组及对照组各27例进行HBIG、无环鸟苷、干扰素联合近、远期抗病毒效应观察。治疗组为无环鸟苷第一周按25~20mg/kg/d计后改17~15mg/kg/d×53天,共60天;人白细胞干扰素1×106U肌注每周3次×4周,后改1.0×106U肌注每周2次×6周,共10周;HBIG400U肌注隔日1次,共10周,对照组仅给予一般“保肝”药物。其中治疗组18例,对照组19例进行治后半年到2年追踪观察,结果近、远期HBcAg、DNAP、HBV-DNA阴转率治疗组均高于对照组,其中治疗组近、远期HBcAg,HBV-DNA阴转率均达40%以上,明显高于对照组(P<0.05~0.01),治疗组近、远期各有4例及2例HBsAg阴转,而对照组则无一例阴转,从近、远期综合抗病毒效应观察,治疗组全阴率分别为33.3%、44.4%,而对照组分别为3.79%及0%,P<0.01,治疗组无明显毒副反应。对比单用无环鸟苷,全阴率31.8%;无环鸟苷加干扰素两药联合全阴率37.5%,均有所提高,达到44.4%,值得进一步研究。 相似文献
44.
我们检测10例普通猪的胄组织,有8例分离到螺杆菌样细菌(HLO)。其菌落、菌体形态和某些生化反应与幽门螺杆菌(HP)相似,但其尿素酶活性较低,HLO全菌蛋白的SDS一pAGE图谱也与HP的不同。本文就HP和HLO及其伴发的人、猪慢性胃炎的特点,作了比较和讨论。 相似文献
45.
本文对106例前列腺标本进行了细菌学研究。慢性前列腺炎厌氧菌检出率为27.3%(29/106)。厌氧菌阳性者中68.9%(20/29)与需氧菌组成混合感染31%(9/29)为单纯厌氧菌感染。研究还提示:厌氧菌感染是慢性前列腺炎不可忽视的原因,氟呱酸对厌氧菌有强大杀灭作用。 相似文献
46.
Ilan Hammel Joseph Alroy Vibha Goyal Stephen J. Galli 《Virchows Archiv. B, Cell pathology including molecular pathology》1993,64(1):83-89
The effect of lysosomal storage diseases on the ultrastructure of human mast cells has not previously been reported. Indeed,
there has been little published evidence indicating that mast cells contain typical lysosomes. However, mast cell cytoplasmic
granules contain hydrolases similar to those found in lysosomes, but which differ from lysosomal hydrolases in exhibiting
optimal activity at higher pH. We therefore examined by transmission electron microscopy the dermal mast cells in 58 biopsies
of patients exhibiting 1 of 29 different lysosomal storage diseases. We found mast cells containing abnormal lysosomes in
16 of these disorders. In 6 of these 16 diseases, the mast cells' cytoplasmic granules appeared normal. These observations
indicate that human mast cells can contain lysosomes, and provide evidence that the enzymes affected by lysosomal storage
diseases are active in mast cells. 相似文献
47.
Protein liquid-liquid phase separation drives the dynamic assembly of membraneless organelles for fulfilling different physiological functions. Under diseased condition, protein may undergo liquid-to-solid condensation to form pathological amyloid aggregates closely associated with neurodegenerative diseases. Chemical probe serves as an important chemical tool not only for exploring the basic principle of the dynamic assembly of different protein condensates in vitro and in cell but also for clinical diagnosis and therapeutics of the related diseases. In this review, we first introduce chemical probes to image and regulate protein condensates. Then, we summarized three different categories of chemical probes including general amyloid dye, selective positron emission tomography tracer, and disaggregating binder, which feature distinct interaction pattern and activity upon binding to different pathological amyloid fibrillar aggregates. Next, we discuss the development of chemical probes for tracking protein amorphous aggregates in cells. Finally, we point out future direction in expanding the probes’ chemical space and applications. 相似文献
48.
49.
Sally Badawi Feda E. Mohamed Divya Saro Varghese Bassam R. Ali 《Traffic (Copenhagen, Denmark)》2023,24(8):312-333
Endoplasmic reticulum-associated protein degradation (ERAD) is a stringent quality control mechanism through which misfolded, unassembled and some native proteins are targeted for degradation to maintain appropriate cellular and organelle homeostasis. Several in vitro and in vivo ERAD-related studies have provided mechanistic insights into ERAD pathway activation and its consequent events; however, a majority of these have investigated the effect of ERAD substrates and their consequent diseases affecting the degradation process. In this review, we present all reported human single-gene disorders caused by genetic variation in genes that encode ERAD components rather than their substrates. Additionally, after extensive literature survey, we present various genetically manipulated higher cellular and mammalian animal models that lack specific components involved in various stages of the ERAD pathway. 相似文献
50.
Pravin Hivare Kratika Mujmer Gitanjali Swarup Sharad Gupta Dhiraj Bhatia 《Traffic (Copenhagen, Denmark)》2023,24(10):434-452
Endocytosis is the fundamental uptake process through which cells internalize extracellular materials and species. Neurodegenerative diseases (NDs) are characterized by a progressive accumulation of intrinsically disordered protein species, leading to neuronal death. Misfolding in many proteins leads to various NDs such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), amyotrophic lateral sclerosis (ALS) and other disorders. Despite the significance of disordered protein species in neurodegeneration, their spread between cells and the cellular uptake of extracellular species is not entirely understood. This review discusses the major internalization mechanisms of the different conformer species of these proteins and their endocytic mechanisms. We briefly introduce the broad types of endocytic mechanisms found in cells and then summarize what is known about the endocytosis of monomeric, oligomeric and aggregated conformations of tau, Aβ, α-Syn, Huntingtin, Prions, SOD1, TDP-43 and other proteins associated with neurodegeneration. We also highlight the key players involved in internalizing these disordered proteins and the several techniques and approaches to identify their endocytic mechanisms. Finally, we discuss the obstacles involved in studying the endocytosis of these protein species and the need to develop better techniques to elucidate the uptake mechanisms of a particular disordered protein species. 相似文献