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981.
982.
Yoon D Kim YJ Cui WY Van der Vaart A Cho YS Lee JY Ma JZ Payne TJ Li MD Park T 《Human genetics》2012,131(6):1009-1021
Diseases related to smoking are the second leading cause of death in the world. Cigarette smoking is a risk factor for several diseases such as cancer and cardiovascular and respiratory disorders. Despite increasing evidence of genetic determination, the susceptibility genes and loci underlying various aspects of smoking behavior are largely unknown. Moreover, almost all reported genome-wide association studies (GWASs) have been performed on samples of European origin, limiting the applicability of the results to other ethnic populations. In this first GWAS on smoking behavior in an Asian population, after analyzing 8,842 DNA samples from the Korea Association Resource project with 352,228 single nucleotide polymorphisms (SNPs) genotyped for each sample, we identified 8 SNPs significantly associated with smoking initiation (SI) and 4 with nicotine dependence (ND). Because of the current unavailability of an independent Asian smoking sample, we replicated the discoveries in independent samples of European-American and African-American origin. Of the 12 SNPs examined in the replicated samples, we identified two SNPs, in the regulator of G-protein signaling 17 gene (rs7747583, p value(meta)?=?6.40?×?10(-6); rs2349433, p value(meta)?=?5.57?×?10(-6)), associated with SI. Also, we found two SNPs significantly associated with ND; one in the FERM domain containing 4A (rs4424567, p value(meta)?=?2.30?×?10(-6)) and the other at 7q31.1 (rs848353, p value(meta)?=?9.16?×?10(-8)). These SNPs represent novel targets for examination of smoking behavior and warrant further investigation using independent samples. 相似文献
983.
Plasmid DNA vaccination is an attractive way to elicit T cell responses against infectious agents and tumor cells. DNA constructs
can be designed to contain multiple T cell epitopes to generate a diverse immune response to incorporate numerous antigens
and to reduce limitations due to MHC restriction into a single entity. We have prepared cDNA plasmid constructs containing
several mouse T cell epitopes connected by either furin-sensitive or furin-resistant linkers and studied the effects of a
cationic cell-penetrating sequence from HIV-tat. Significant CD8 T cell responses were obtained with multi-epitope DNA vaccines
followed by in vivo electroporation regardless of the type of linker used and whether the construct had the HIV-tat sequence.
The magnitude of immune responses was very similar to all CD8 T cell epitopes contained within each vaccine construct, indicating
the absence of immunodominance. Incorporating a T helper epitope into the constructs increased the T cell responses. Prophylactic
and therapeutic antitumor responses against B16 melanoma were obtained using a construct containing epitopes from melanosomal
proteins, indicating that this vaccination was successful in generating responses to self-antigens that potentially may be
subjected to immune tolerance. These findings are useful for designing DNA vaccines for a multitude of diseases where T lymphocytes
play a protective or therapeutic role. 相似文献
984.
Anaerobic gram-negative oral bacteria such as Treponema denticola, Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Tannerella forsythia, Campylobacter rectus, and Fusobacterium nucleatum are closely associated with periodontal diseases. We measured the relative population (bacterial levels) of these oral pathogens in subgingival tissues of patients at different stages of Korean chronic periodontal diseases. We divided the individuals into those with chronic gingivitis (G), moderate periodontitis (P1), severe periodontitis (P2), and normal individuals (N) (n?=?20 for each group) and subgingival tissue samples were collected. We used real-time PCR with TaqMan probes to evaluate the change of periodontal pathogens among different stages of periodontitis. Bacterial levels of A. actinomycetemcomitans and C. rectus are significantly increased in individuals with chronic gingivitis and moderate periodontitis, but unchanged in severe periodontitis patients. These results suggest that analyzing certain bacterial levels among total oral pathogens may facilitate understanding of the role of periodontal bacteria in the early stages of periodontitis. 相似文献
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Kim N Yoo JC Han JY Hwang EM Kim YS Jeong EY Sun CH Yi GS Roh GS Kim HJ Kang SS Cho GJ Park JY Choi WS 《Journal of cellular physiology》2012,227(3):1157-1167
Clusterin (CLU), a glycoprotein, is involved in apoptosis, producing two alternatively spliced isoforms in various cell types. The pro-apoptotic CLU appears to be a nuclear isoform (nuclear clusterin; nCLU), and the secretory CLU (sCLU) is thought to be anti-apoptotic. The detailed molecular mechanism of nCLU as a pro-apoptotic molecule has not yet been clear. In the current study, overexpressed nCLU induced apoptosis in human kidney cells. Biochemical studies revealed that nCLU sequestered Bcl-XL via a putative BH3 motif in the C-terminal coiled coil (CC2) domain, releasing Bax, and promoted apoptosis accompanied by activation of caspase-3 and cytochrome c release. These results suggest a novel mechanism of apoptosis mediated by nCLU as a pro-apoptotic molecule. 相似文献
990.
Kim JH Lee ER Jeon K Choi HY Lim H Kim SJ Chae HJ Park SH Kim S Seo YR Kim JH Cho SG 《Biochimica et biophysica acta》2012,1823(4):876-888
Bax Inhibitor-1 (BI-1) is an evolutionally conserved apoptotic suppressor and belongs to the BI-1 family of proteins, which contain BI-1-like transmembrane domains. As their cellular functions and regulatory mechanisms remain incompletely understood, we compared their anti-apoptotic properties. Forced expression of BI-1 resulted in the most effective suppression of stress-induced apoptosis, compared with other family members, together with significant extracellular signal-regulated kinase (ERK)1/2 activation. BI-1-mediated ERK1/2 activation led to the suppression of mitochondria-mediated reactive oxygen species (ROS) production. Involvement of the ERK signaling pathway in BI-1-induced anti-apoptotic effects was confirmed by knockdown studies with ERK- or BI-1-specific siRNA. Moreover, we produced transgenic (TG) mice overexpressing BI-1, and the relationship between ERK1/2 activation and the suppression of ROS production or apoptosis was confirmed in mouse embryonic fibroblast (MEF) cells derived from these mice. Interestingly, we found that BI-1 TG mice showed splenomegaly and abnormal megakaryopoiesis. Taken together, our results suggest that BI-1-induced ERK1/2 activation plays an important role in the modulation of intracellular ROS generation and apoptotic cell death and may also affect autoimmune response. 相似文献