全文获取类型
收费全文 | 5582篇 |
免费 | 539篇 |
国内免费 | 117篇 |
专业分类
6238篇 |
出版年
2023年 | 46篇 |
2022年 | 95篇 |
2021年 | 171篇 |
2020年 | 101篇 |
2019年 | 119篇 |
2018年 | 131篇 |
2017年 | 91篇 |
2016年 | 166篇 |
2015年 | 322篇 |
2014年 | 337篇 |
2013年 | 408篇 |
2012年 | 491篇 |
2011年 | 441篇 |
2010年 | 256篇 |
2009年 | 208篇 |
2008年 | 310篇 |
2007年 | 251篇 |
2006年 | 245篇 |
2005年 | 229篇 |
2004年 | 199篇 |
2003年 | 174篇 |
2002年 | 169篇 |
2001年 | 107篇 |
2000年 | 121篇 |
1999年 | 108篇 |
1998年 | 67篇 |
1997年 | 49篇 |
1996年 | 36篇 |
1995年 | 36篇 |
1994年 | 43篇 |
1993年 | 41篇 |
1992年 | 70篇 |
1991年 | 56篇 |
1990年 | 45篇 |
1989年 | 55篇 |
1988年 | 50篇 |
1987年 | 35篇 |
1986年 | 39篇 |
1985年 | 30篇 |
1984年 | 50篇 |
1983年 | 27篇 |
1982年 | 27篇 |
1981年 | 22篇 |
1980年 | 15篇 |
1979年 | 27篇 |
1978年 | 24篇 |
1977年 | 20篇 |
1975年 | 16篇 |
1974年 | 9篇 |
1971年 | 11篇 |
排序方式: 共有6238条查询结果,搜索用时 15 毫秒
841.
A non-invasive diagnostic approach is crucial for the evaluation of severity of liver disease, treatment decisions, and assessing
drug efficacy. This study evaluated plasma proteomic profiling via an N-terminal isotope tagging strategy coupled with liquid
chromatography/Fourier transform ion cyclotron resonance mass spectrometry measurement to detect liver fibrosis staging. Pooled
plasma from different liver fibrosis stages, which were assessed in advance by the current gold-standard of liver biopsy,
was quantitatively analyzed. A total of 72 plasma proteins were found to be dysregulated during the fibrogenesis process,
and this finding constituted a valuable candidate plasma biomarker bank for follow-up analysis. Validation results of fibronectin
by Western blotting reconfirmed the mass-based data. Ingenuity Pathways Analysis showed four types of metabolic networks for
the functional effect of liver fibrosis disease in chronic hepatitis B patients. Consequently, quantitative proteomics via
the N-terminal acetyl isotope labeling technique provides an effective and useful tool for screening plasma candidate biomarkers
for liver fibrosis. We quantitatively monitored the fibrogenesis process in CHB patients. We discovered many new valuable
candidate biomarkers for the diagnosis of liver fibrosis and also partly identified the mechanism involved in liver fibrosis
disease. These results provide a clearer understanding of liver fibrosis pathophysiology and will also hopefully lead to improvement
of clinical diagnosis and treatment. 相似文献
842.
843.
Objective
To describe the epidemiological characteristics of infantile hypertrophic pyloric stenosis (IHPS) in ethnic Chinese children.Materials and Methods
We reviewed the National Health Insurance claims database and analyzed data from children less than one year of age who had been diagnosed with IHPS (ICD-9-CM 750.5) and had undergone pyloromyotomy (ICD-9-CM 43.3). We analyzed the incidence, gender, age at diagnosis, length of hospital stay, seasonal variation and cost of IHPS from data collected between January 1997 and December 2007.Results
A total of 1,077 infants met inclusion criteria, including 889 boys and 188 girls. The annual incidence of IHPS ranged from 0.30 to 0.47 per 1,000 live births with a mean incidence of 0.39 per 1,000 live births. Between 2002 and 2007, the incidence showed a declining trend (P = 0.025) with coincidentally increasing trends for both exclusive breastfeeding (P = 0.014) and breastfeeding plus bottle feeding (P = 0.004). The male-to-female rate ratio was dynamic and increased from 3.03 during the first two weeks of life to 8.94 during the 8th through 10thweeks of life. The overall male-to-female rate ratio was 4.30. The mean age at diagnosis was 43.1±2.4 days. After analyzing the months of birth and hospital admission, no seasonal variation associated with IHPS was detected. The mean length of hospital stay was 8.28±7.10 days.Conclusions
The incidence of IHPS in Taiwan, a country with a majority ethnic Chinese population, was lower than observed incidences in Caucasian populations living in Western countries. Breastfeeding campaigns and low maternal smoking rates may contribute to the lower incidence of IHPS in Taiwan. However, additional studies with longer follow-up periods are needed. 相似文献844.
Regulation of cyclin levels is important for many cell cycle-related processes and can occur at several different steps of gene expression. Translational regulation of cyclins, which occurs by a variety of regulatory mechanisms, permits a prompt response to signal transduction pathways induced by environmental stimuli. This review will summarize translational control of cyclins and its influence on cell cycle progression. 相似文献
845.
The halophilic methanoarchaeon Methanohalophilus portucalensis can synthesize the osmolyte betaine de novo in response to extracellular salt stress. Betaine is generated by the stepwise methylation of glycine to form sarcosine, N, N-dimethylglycine and betaine by using S-adenosyl-L-methionine (AdoMet) as the methyl donor. The complete gene cluster of Mpgsmt-sdmt was cloned from Southern hybridization and heterologous expressed in E. coli respectively. The recombinant MpGSMT and MpSDMT both retained their in vivo functional activities in E. coli BL21(DE3)RIL to synthesize and accumulate betaine and conferred elevated survival ability in betaine transport deficient mutant E. coli MKH13 under high salt stress. The dramatic activating effects of sodium and potassium ions on the in vitro methyltransferase activities of MpGSMT, but not MpSDMT or bacterial GSMT and SDMT, revealed that GSMT from halophilic methanoarchaeon possesses novel regulate mechanism in betaine biosynthesis pathway. The circular dichroism spectra showed the fluctuated peaks at 206 nm were detected in the MpGSMT under various concentrations of potassium or sodium ions. This fluctuated difference may cause by a change in the β-turn structure located at the conserved glycine- and sarcosine-binding residue Arg167 of MpGSMT. The analytical ultracentrifugation analysis indicated that the monomer MpGSMT switched to dimeric form increased from 7.6% to 70% with KCl concentration increased from 0 to 2.0 M. The level of potassium and sodium ions may modulate the substrate binding activity of MpGSMT through the conformational change. Additionally, MpGSMT showed a strong end product, betaine, inhibitory effect and was more sensitive to the inhibitor AdoHcy. The above results indicated that the first enzymatic step involved in synthesizing the osmolyte betaine in halophilic archaea, namely, GSMT, may also play a major role in coupling the salt-in and compatible solute (osmolyte) osmoadaptative strategies in halophilic methanogens for adapting to high salt environments. 相似文献
846.
Ruye Ma Dandan Yu Yu Peng Hongfei Yi Yingcong Wang Taofang Cheng Bingqing Shi Guang Yang Weiming Lai Xiaosong Wu Ye Lu Jumei Shi 《Acta biochimica et biophysica Sinica》2021,(6):775-783
Resveratrol,a natural compound extracted from the skins of grapes,berries,or other fruits,has been shown to have anti-tumor effects against multiple myeloma(MM)... 相似文献
847.
848.
Nguyen Thi Nha Trang Chao-Yang Lai Hsiao-Chi Tsai Yuan-Li Huang Shan-Chi Liu Chun-Hao Tsai Yi-Chin Fong Huey-En Tzeng Chih-Hsin Tang 《International journal of biological sciences》2023,19(2):412
Osteosarcoma is a highly mortal bone tumor, with a high metastatic potential, promoted in part by the enzyme procollagen-lysine 2-oxoglutarate 5-dioxygenase 2 (PLOD2). Increasing level of PLOD2 in osteosarcoma tissue correlates with lymphatic and distant metastasis. The adipokine apelin (APLN) is also found in different cancers and APLN upregulation promotes angiogenesis and metastasis, but its effects on osteosarcoma metastasis are uncertain. We explored APLN functioning in metastatic osteosarcoma. An analysis of records from the Gene Expression Omnibus (GEO) database showed higher levels of APLN expression in osteosarcoma tissue than in normal tissue. Similarly, levels of APLN and PLOD2 mRNA synthesis were upregulated in osteosarcoma tissue. Levels of APLN and PLOD2 protein correlated positively with osteosarcoma clinical stages. APLN increased PLOD2 expression in human osteosarcoma cell lines and cell migration via the mammalian Sterile 20-like kinase 1 (MST1), monopolar spindle-one-binder protein (MOB)1, and YAP cascades, and through hsa_circ_0000004 functioning as a sponge of miR-1303. We also found that knockdown of APLN antagonized lung metastasis in mice with osteosarcoma. APLN may be a therapeutic target in osteosarcoma metastasis. 相似文献
849.
RaiHua Lai ChihCheng Hsu BenHui Yu YuRu Lo YuehYing Hsu MeiHsin Chen JyhLyh Juang 《Aging cell》2022,21(8)
Vitamin D deficiency has been epidemiologically linked to Alzheimer''s disease (AD) and other dementias, but no interventional studies have proved causality. Our previous work revealed that the genomic vitamin D receptor (VDR) is already converted into a non‐genomic signaling pathway by forming a complex with p53 in the AD brain. Here, we extend our previous work to assess whether it is beneficial to supplement AD mice and humans with vitamin D. Intriguingly, we first observed that APP/PS1 mice fed a vitamin D‐sufficient diet showed significantly lower levels of serum vitamin D, suggesting its deficiency may be a consequence not a cause of AD. Moreover, supplementation of vitamin D led to increased Aβ deposition and exacerbated AD. Mechanistically, vitamin D supplementation did not rescue the genomic VDR/RXR complex but instead enhanced the non‐genomic VDR/p53 complex in AD brains. Consistently, our population‐based longitudinal study also showed that dementia‐free older adults (n = 14,648) taking vitamin D3 supplements for over 146 days/year were 1.8 times more likely to develop dementia than those not taking the supplements. Among those with pre‐existing dementia (n = 980), those taking vitamin D3 supplements for over 146 days/year had 2.17 times the risk of mortality than those not taking the supplements. Collectively, these animal model and human cohort studies caution against prolonged use of vitamin D by AD patients. 相似文献
850.
Takashi Yamamoto Padma Nair Shou-wu Ma Peg Davis Henry I. Yamamura Todd W. Vanderah Frank Porreca Josephine Lai Victor J. Hruby 《Bioorganic & medicinal chemistry》2009,17(20):7337-7343
In order to improve metabolic stability, a ring structure with a cystine moiety was introduced into TY027 (Tyr-d-Ala-Gly-Phe-Met-Pro-Leu-Trp-NH-[3′,5′-(CF3)2Bzl]), which is a lead compound of our developing bifunctional peptide possessing opioid agonist and NK1 antagonist activities. TY038 (Tyr-cyclo[d-Cys-Gly-Phe-Met-Pro-d-Cys]-Trp-NH-[3′,5′-(CF3)2Bzl]) was found as a highly selective δ opioid agonist over μ receptor in conventional tissue-based assays, together with an effective NK1 antagonist activity and good metabolic stability with more than 24 h half life in rat plasma. 相似文献