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21.
Many deterministic models of sexually transmitted diseases, as well as population models in general, contain elements of stochastic or statistical reasoning. An example of such a model is that of Dietz and Hadeler (1988) concerning sexually transmitted diseases in which there is partnership formation and dissolution. Among the interesting formulas in this paper, which enter into the analysis of the model, are those for the expected number of partners a male or female has during a lifetime. To a probabilist such formulas suggest the possibility that some stochastic process may be constructed so as to yield these formulas as well as others that may be of interest. The principal purpose of this paper is to demonstrate that such a stochastic process does indeed exist in the form of a three state semi-Markov process in continuous time with stationary laws of evolution and with a one-step density matrix determined by four parameters which were interpreted as constant latent risk functions in the classical theory of competing risks. This construction of a semi-Markov process not only provides a framework for the systematic derivation of the formulas of Dietz and Hadeler but also suggests pathways,for extensions to the age-dependent case.This research was partially supported by NATO Grant D.890350 相似文献
22.
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
23.
R. W. Wilson E. W. Taylor 《Journal of comparative physiology. B, Biochemical, systemic, and environmental physiology》1993,163(3):239-246
Rainbow trout, Oncorhynchus mykiss, acclimated to 33% sea water (12 mg·ml-1 salinity) experienced significant (10 meq·1-1) increases in plasma [Na+] and [Cl-] within 5 h of exposure to 6.3 mol copper·1-1 indicating severe impairment of branchial ionoregulatory capacity. All plasma ion levels subsequently stabilised once the transbranchial [Na+] gradient was reduced to zero. The similar ionic strength of the external medium and their body fluids appeared to protect trout maintained in 33% sea water from further ionoregulatory stress and any secondary physiological disturbances during exposure to copper. Despite three- and fourfold greater transbranchial [Na+] and [Cl-] gradients, trout acclimated to full-strength sea water (35 mg·ml-1 salinity) suffered no major changes in plasma Na+, Cl-, K+, or Ca2+, blood gases or haematology during 24 h exposure to 6.3 mol copper·1-1. This reduction in toxicity in full strength sea water cannot be explained by differences in copper speciation. We suggest that during acute exposure to waterborne copper, active NaCl extrusion is unaffected due to the basolateral location of the gill Na+/K+-ATPase, but that ionoregulatory disturbances can occur due to gill permeability changes secondary to the displacement of surface-bound Ca2+. However, in full strength sea water the three-fold higher ambient [Ca2+] and [Mg2+] appear to be sufficient to prevent any detrimental permeability changes in the presence of 6.3 mol copper·1-1. Plasma [NH
+
4
] and [HCO
-
3
] were both significantly elevated during exposure to copper, indicating that some aspects of gill ion transport (specifically the apical Na+/NH
+
4
and Cl-/HCO
-
3
exchanges involved in acid/base regulation and nitrogenous waste excretion) are vulnerable to inhibition in the presence of waterborne copper.Abbreviations
C
aO2
arterial oxygen content
- Hb
haemoglobin
- Hct
haematocrit
- MABP
mean arterial blood pressure
- MCHC
mean cell haemoglobin content
-
MO2
rate of oxygen consumption
-
P
a
CO2
arterial carbon dioxide tension
-
P
aO2
arterial oxygen partial pressure
- S
salinity
- SW
sea water
-
T
Amm
total ammonia (=NH3+NH
+
4
)
-
T
CO
2
total carbon dioxide
- TEP
transepithelial potential
- TOC
total organic carbon
- %Hb-O2
percentage of haemoglobin saturated with oxygen 相似文献
24.
降钙素基因相关肽的研究进展 总被引:1,自引:0,他引:1
吴祥声 《氨基酸和生物资源》1994,(1)
降钙素基因相关肽(CGRP)是由37个氨基酸残基构成的生物活性多肽,与降钙素(CT)源子一个共同的基因。CGRP分布广泛,具有很强的血管扩张、降低血压以及心肌正性肌力作用等,并参与心血管系统稳态的调节。目前,CGRP已能人工合成,将为某些心血管疾病如高血压、心肌缺血、痉挛性或闭塞性周围血管疾病等的治疗提供一条崭新的途径。 相似文献
25.
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
26.
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
27.
28.
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
29.
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
30.
Shawn Thatcher April Leonard Marianna Lauer Gayathri Panangipalli Bret Norman Zhenglin Hou Victor Llaca Wang-Nan Hu Xiuli Qi Jennifer Jaqueth Dina Severns David Whitaker Bill Wilson Girma Tabor Bailin Li 《Molecular Plant Pathology》2023,24(7):758-767
Northern corn leaf blight, caused by the fungal pathogen Exserohilum turcicum, is a major disease of maize. The first major locus conferring resistance to E. turcicum race 0, Ht1, was identified over 50 years ago, but the underlying gene has remained unknown. We employed a map-based cloning strategy to identify the Ht1 causal gene, which was found to be a coiled-coil nucleotide-binding, leucine-rich repeat (NLR) gene, which we named PH4GP-Ht1. Transgenic testing confirmed that introducing the native PH4GP-Ht1 sequence to a susceptible maize variety resulted in resistance to E. turcicum race 0. A survey of the maize nested association mapping genomes revealed that susceptible Ht1 alleles had very low to no expression of the gene. Overexpression of the susceptible B73 allele, however, did not result in resistant plants, indicating that sequence variations may underlie the difference between resistant and susceptible phenotypes. Modelling of the PH4GP-Ht1 protein indicated that it has structural homology to the Arabidopsis NLR resistance gene ZAR1, and probably forms a similar homopentamer structure following activation. RNA sequencing data from an infection time course revealed that 1 week after inoculation there was a threefold reduction in fungal biomass in the PH4GP-Ht1 transgenic plants compared to wild-type plants. Furthermore, PH4GP-Ht1 transgenics had significantly more inoculation-responsive differentially expressed genes than wild-type plants, with enrichment seen in genes associated with both defence and photosynthesis. These results demonstrate that the NLR PH4GP-Ht1 is the causal gene underlying Ht1, which represents a different mode of action compared to the previously reported wall-associated kinase northern corn leaf blight resistance gene Htn1/Ht2/Ht3. 相似文献