全文获取类型
收费全文 | 7718篇 |
免费 | 676篇 |
国内免费 | 922篇 |
出版年
2024年 | 34篇 |
2023年 | 151篇 |
2022年 | 288篇 |
2021年 | 555篇 |
2020年 | 405篇 |
2019年 | 472篇 |
2018年 | 420篇 |
2017年 | 346篇 |
2016年 | 392篇 |
2015年 | 569篇 |
2014年 | 672篇 |
2013年 | 635篇 |
2012年 | 796篇 |
2011年 | 637篇 |
2010年 | 418篇 |
2009年 | 330篇 |
2008年 | 330篇 |
2007年 | 302篇 |
2006年 | 235篇 |
2005年 | 213篇 |
2004年 | 149篇 |
2003年 | 115篇 |
2002年 | 135篇 |
2001年 | 104篇 |
2000年 | 72篇 |
1999年 | 77篇 |
1998年 | 66篇 |
1997年 | 48篇 |
1996年 | 43篇 |
1995年 | 36篇 |
1994年 | 47篇 |
1993年 | 25篇 |
1992年 | 22篇 |
1991年 | 24篇 |
1990年 | 25篇 |
1989年 | 26篇 |
1988年 | 17篇 |
1987年 | 20篇 |
1986年 | 17篇 |
1985年 | 10篇 |
1984年 | 7篇 |
1983年 | 6篇 |
1982年 | 3篇 |
1981年 | 2篇 |
1980年 | 3篇 |
1979年 | 3篇 |
1973年 | 2篇 |
1970年 | 2篇 |
1968年 | 2篇 |
1953年 | 1篇 |
排序方式: 共有9316条查询结果,搜索用时 15 毫秒
961.
Trpm8 (melastatin-related transient receptor potential member 8), a member of the transient receptor potential (TRP) superfamily,
encoding a cation channel named TRPM8, has been shown to be a primary androgen-responsive gene and play an important role
in prostate physiology. To investigate the expression feature of TRPM8 in urogenital tract of male rats, and whether TRPM8
was also regulated by androgen receptor in these organs, male Sprague–Dawley rats were divided into three groups of 35 animals
as follows: sham-operated (SHAM), orchidectomized (ORX), orchidectomized plus DHT treatment (O + D). Organs in urogenital
tract, including kidney, prostate, seminal vesicle (SV), testis, epididymis and penis, were collected at different post-castration
periods. RT-PCR, real-time PCR and Western blotting were used to detect the expression of androgen receptor (AR) and trpm8
in these tissue. As a result, AR and trpm8 can be detected in all these organs at mRNA or/and protein level. The mRNA expression
of trpm8 in kidney, prostate, SV and penis decreased 24 or 72 h after castration and kept decreasing in a time-dependant manner.
However, treatment of dihydrotestosterone (DHT) could reverse the effect of surgical castration. Collectively, our data provide
evidence that TRPM8 and AR were expressed generally in urogenital tract of male rats, and in these organs, expression of trpm8
was regulated by serum androgen. 相似文献
962.
Toll-like receptors (TLRs) have been found to contribute to the pathogenesis of rheumatoid arthritis (RA). The aim of this
study is to investigate the regulation and potential role of TLR2 in spleen of pristane-induced arthritis (PIA) rat, which
can be used to further understand the mechanisms of RA. Arthritis in DA rats was induced by pristane. TLR2 expression in spleen
was detected by real-time quantitative PCR and western blotting, and TLR2 expression at both mRNA and protein levels was upregulated
in PIA rats. Peptidoglycan (PGN) was systemically administrated to PIA rats, and arthritis severity was evaluated macroscopically
and microscopically. Results showed that systemic administration of PGN to PIA rats obviously deteriorated arthritis severity.
TLR2 expression on splenocytes and different types of immune cells was measured by flow cytometry. And it was found that TLR2
was mainly expressed on antigen-presenting cells (APCs) of spleen, and the proportion of TLR2+ dendritic cells and macrophages in spleen of PIA rats was increased remarkably. Thus, we conclude that the induction of TLR2+ APCs in spleen may participate in the maintenance of PIA. 相似文献
963.
Qunying Wu Sen Lu Ling Wang Jiaojiao Hu Fengchang Qiao Xuemei Qiu Chengcheng Zhao Yingbin Lao Yunwei Song Hong Fan 《Molecular biology reports》2012,39(12):10949-10955
DNA-methyltransferase (DNMT)-3A plays a crucial role in embryonic development and aberrant DNA methylation in carcinogenesis. Polymorphisms of the DNMT3A gene may influence its enzymatic activity and its contribution to susceptibility to cancer. This study evaluated the association of DNMT3A rs36012910 A>G with susceptibility to gastric cancer (GC) in a Chinese population. Genomic DNA was extracted from samples taken from 340 patients with GC and 251 healthy control subjects. The genotype frequency of DNMT3A rs36012910 A>G in all subjects was detected by polymerase chain reaction–restriction fragment length polymorphism and confirmed by sequencing. Stratification analyses were used to study subgroups by age and gender and to evaluate the association of rs36012910 A>G polymorphism with genetic susceptibility to GC. All patients and control individuals were successfully genotyped for the DNMT3A rs36012910 A>G polymorphism. The frequency of DNMT3A rs36012910 allele G is 3.39?% in healthy individuals and 7.78?% in GC patients, respectively. The rs36012910 AG genotype was significantly more common in the GC group than in the controls, although the rs36012910 GG genotype was only one case in GC patients. Further stratification indicated that AG+GG genotypes were associated with susceptibility to GC in males older than 60, but this polymorphism has no significant association with GC susceptibility in females. Male individuals who carried AG+GG genotypes had a 2.362-fold increased risk of GC compared to those who carried the AA genotype. The rs36012910 allele G was associated with an increased risk of GC compared to the rs36012910 allele A. This is the first report to investigate the distribution and evaluate the association of a rare SNP in DNMT3A with genetic susceptibility to GC. DNMT3A rs36012910 A>G might become a potential biomarker for use in GC prediction, although further studies in larger groups and different populations are needed for confirmation. 相似文献
964.
Chen X Yu Z Guo L Li L Meng H Wang D Liu R Liu J 《Experimental & applied acarology》2012,56(2):143-150
The paper investigated the life cycle of the hard tick Haemaphysalis doenitzi under laboratory conditions and its phylogeny based on mitochondrial 16S rDNA. The results revealed that the complete life
cycle of H. doenitzi requires a mean duration of 109.6 days ranging from 91 to 137 days and the average prefeeding, feeding and premoulting periods
of larvae, nymphs and females and the eggs hatching period are 18.7, 26.9, 38.9, and 25.1 days, respectively. In addition,
the weight of engorged females is highly correlated with the number of egg masses laid (r = 0.936, P < 0.001). The female reproductive efficiency index and reproductive fitness index are 13.4 and 12.8, respectively. The mean
weight of the engorged nymphs (2.77 mg) moulting to females is much higher than those (1.68 mg) moulting to males, which could
be used as an index to predict sexes in this species. The ratio of male to female is 1:1.01. Moreover, multisequence alignments
and phylogenetic tree constructed based on the mitochondrial 16S rDNA sequences suggest that H. doenitzi is genetically close to H. longicornis. 相似文献
965.
Gong M Xia M Zhang J Gu J Liu X Cheng J 《Applied microbiology and biotechnology》2012,93(3):1097-1108
A novel antitumor protein, designated RE26, with anti-lymphoma activity was purified from a Tris–HCl buffer extract of Rozites emodensis (Berk.) Moser by three successive steps of ion exchange chromatography. SDS-PAGE and gel filtration chromatography revealed
that RE26 is a monomeric protein of 26 kDa, and isoelectrofocusing assay indicated its isoelectric point of 4.3–4.4. RE26
has high stability over a wide pH range (pH 3–11) but is sensitive to temperature and only stable under 40 °C. Partial amino
acid sequences of two RE26 peptide fragments were determined by Edman degradation as GLEEEETLLLLFFPP and GTEQE. The half-maximal
inhibitory concentration (IC50) of RE26 against tested lymphoma cell lines was around 4 μg/ml. In vitro experiments showed that RE26 could specifically
bind to lymphoma cells; activate the caspases, including caspases 3, 8, and 9 in host cells; and induce apoptosis. Experiments
in nude mice indicated local RE26 injection adjacent to tumor site could inhibit lymphoma formation. 相似文献
966.
aaRSs (aminoacyl-tRNA synthetases) establish the rules of the genetic code by catalysing the formation of aminoacyl-tRNA. The quality control for aminoacylation is achieved by editing activity, which is usually carried out by a discrete editing domain. For LeuRS (leucyl-tRNA synthetase), the CP1 (connective peptide 1) domain is the editing domain responsible for hydrolysing mischarged tRNA. The CP1 domain is universally present in LeuRSs, except MmLeuRS (Mycoplasma mobile LeuRS). The substitute of CP1 in MmLeuRS is a nonapeptide (MmLinker). In the present study, we show that the MmLinker, which is critical for the aminoacylation activity of MmLeuRS, could confer remarkable tRNA-charging activity on the inactive CP1-deleted LeuRS from Escherichia coli (EcLeuRS) and Aquifex aeolicus (AaLeuRS). Furthermore, CP1 from EcLeuRS could functionally compensate for the MmLinker and endow MmLeuRS with post-transfer editing capability. These investigations provide a mechanistic framework for the modular construction of aaRSs and their co-ordination to achieve catalytic efficiency and fidelity. These results also show that the pre-transfer editing function of LeuRS originates from its conserved synthetic domain and shed light on future study of the mechanism. 相似文献
967.
Intraperitoneal (i.p.) administration of the synthetic agonist of the glucagon like peptide-1 (GLP-1) receptor exenatide reduces food intake. Here, we evaluated possible peripheral pathways for this reduction. Exenatide (0.5 μg/kg, i.p.) was given to three, overnight food-deprived, groups of rats: total subdiaphragmatic vagotomy (VGX, severs the vagus nerve), celiaco-mesenteric ganglionectomy (CMGX, severs the splanchnic nerve) and combined VGX/CMGX. Following the injection, meal sizes (MSs) and intermeal intervals (IMIs) were determined for a total of 120 min. We found that exenatide reduced the sizes of the first two meals but failed to prolong the IMI between them, that VGX attenuated the reduction of the first MS, and that VGX, CMGX and combined VGX/CMGX attenuated the reduction of the second MS by exenatide. Therefore, the vagus nerve appears necessary for the reduction of the first MS by exenatide, whereas both nerves appear necessary for the reduction of the second MS by this peptide. 相似文献
968.
Cui X Wang Y Meng L Fei W Deng J Xu G Peng X Ju S Zhang L Liu G Zhao L Yang H 《American journal of physiology. Endocrinology and metabolism》2012,302(6):E705-E713
Berardinelli-Seip congenital lipodystrophy type 2 (BSCL2) is a recessive disorder characterized by an almost complete loss of adipose tissue, insulin resistance, and fatty liver. BSCL2 is caused by loss-of-function mutations in the BSCL2/seipin gene, which encodes seipin. The essential role for seipin in adipogenesis has recently been established both in vitro and in vivo. However, seipin is highly upregulated at later stages of adipocyte development, and its role in mature adipocytes remains to be elucidated. We therefore generated transgenic mice overexpressing a short isoform of human BSCL2 gene (encoding 398 amino acids) using the adipocyte-specific aP2 promoter. The transgenic mice produced ~150% more seipin than littermate controls in white adipose tissue. Surprisingly, the increased expression of seipin markedly reduced the mass of white adipose tissue and the size of adipocytes and lipid droplets. This may be due in part to elevated lipolysis rates in the transgenic mice. Moreover, there was a nearly 50% increase in the triacylglycerol content of transgenic liver. These results suggest that seipin promotes the differentiation of preadipocytes but may inhibit lipid storage in mature adipocytes. 相似文献
969.
970.
利用木质纤维素生产燃料乙醇的过程中,前期预处理所产生的抑制剂会影响酵母的正常生长和后续的发酵过程。为减小抑制剂的影响所采取的一些脱毒策略往往造成糖的损失和生产成本的增加,这在实际生产与经济上是不可行的。因此,具有强的抑制剂耐受性的酿酒酵母菌株对于提高纤维素乙醇产率是十分重要的。近十年来,对于酿酒酵母胁迫耐受机制的研究取得了一些重要的进展,着重介绍目前酿酒酵母对抑制剂耐受机制的研究现状,包括一些关键性基因的表达及代谢通路过程分析等。同时也介绍一些应对抑制剂提高酵母发酵能力的措施。 相似文献