全文获取类型
收费全文 | 10017篇 |
免费 | 842篇 |
国内免费 | 1387篇 |
出版年
2024年 | 29篇 |
2023年 | 156篇 |
2022年 | 355篇 |
2021年 | 605篇 |
2020年 | 450篇 |
2019年 | 538篇 |
2018年 | 488篇 |
2017年 | 315篇 |
2016年 | 434篇 |
2015年 | 664篇 |
2014年 | 792篇 |
2013年 | 799篇 |
2012年 | 1016篇 |
2011年 | 934篇 |
2010年 | 516篇 |
2009年 | 535篇 |
2008年 | 621篇 |
2007年 | 488篇 |
2006年 | 429篇 |
2005年 | 358篇 |
2004年 | 272篇 |
2003年 | 211篇 |
2002年 | 158篇 |
2001年 | 133篇 |
2000年 | 112篇 |
1999年 | 144篇 |
1998年 | 87篇 |
1997年 | 100篇 |
1996年 | 65篇 |
1995年 | 56篇 |
1994年 | 51篇 |
1993年 | 45篇 |
1992年 | 50篇 |
1991年 | 42篇 |
1990年 | 41篇 |
1989年 | 30篇 |
1988年 | 25篇 |
1987年 | 19篇 |
1986年 | 30篇 |
1985年 | 21篇 |
1984年 | 9篇 |
1983年 | 10篇 |
1982年 | 3篇 |
1981年 | 1篇 |
1980年 | 2篇 |
1979年 | 3篇 |
1974年 | 1篇 |
1973年 | 1篇 |
1971年 | 1篇 |
1950年 | 1篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
961.
Qian Jiang Stacey Arnold Tiffany Heanue Krishna?Praneeth Kilambi Betty Doan Ashish Kapoor Albee?Yun Ling Maria?X. Sosa Moltu Guy Qingguang Jiang Grzegorz Burzynski Kristen West Seneca Bessling Paola Griseri Jeanne Amiel Raquel?M. Fernandez Joke?B.G.M. Verheij Robert?M.W. Hofstra Salud Borrego Stanislas Lyonnet Isabella Ceccherini Jeffrey?J. Gray Vassilis Pachnis Andrew?S. McCallion Aravinda Chakravarti 《American journal of human genetics》2015,96(4):581-596
Innervation of the gut is segmentally lost in Hirschsprung disease (HSCR), a consequence of cell-autonomous and non-autonomous defects in enteric neuronal cell differentiation, proliferation, migration, or survival. Rare, high-penetrance coding variants and common, low-penetrance non-coding variants in 13 genes are known to underlie HSCR risk, with the most frequent variants in the ret proto-oncogene (RET). We used a genome-wide association (220 trios) and replication (429 trios) study to reveal a second non-coding variant distal to RET and a non-coding allele on chromosome 7 within the class 3 Semaphorin gene cluster. Analysis in Ret wild-type and Ret-null mice demonstrates specific expression of Sema3a, Sema3c, and Sema3d in the enteric nervous system (ENS). In zebrafish embryos, sema3 knockdowns show reduction of migratory ENS precursors with complete ablation under conjoint ret loss of function. Seven candidate receptors of Sema3 proteins are also expressed within the mouse ENS and their expression is also lost in the ENS of Ret-null embryos. Sequencing of SEMA3A, SEMA3C, and SEMA3D in 254 HSCR-affected subjects followed by in silico protein structure modeling and functional analyses identified five disease-associated alleles with loss-of-function defects in semaphorin dimerization and binding to their cognate neuropilin and plexin receptors. Thus, semaphorin 3C/3D signaling is an evolutionarily conserved regulator of ENS development whose dys-regulation is a cause of enteric aganglionosis. 相似文献
962.
963.
964.
Vincent J. Cannistraro Santhi Pondugula Qian Song John-Stephen Taylor 《The Journal of biological chemistry》2015,290(44):26597-26609
Sunlight-induced C to T mutation hot spots in skin cancers occur primarily at methylated CpG sites that coincide with sites of UV-induced cyclobutane pyrimidine dimer (CPD) formation. The C and 5-methyl-C in CPDs are not stable and deaminate to U and T, respectively, which leads to the insertion of A by the DNA damage bypass polymerase η, thereby defining a probable mechanism for the origin of UV-induced C to T mutations. Deamination rates for TmCG CPDs have been found to vary 12-fold with rotational position in a nucleosome in vitro. To determine the influence of nucleosome structure on deamination rates in vivo, we determined the deamination rates of CPDs at TCG sites in a stably positioned nucleosome within the FOS promoter in HeLa cells. A procedure for in vivo hydroxyl radical footprinting with Fe-EDTA was developed, and, together with results from a cytosine methylation protection assay, we determined the translational and rotational positions of the TCG sites. Consistent with the in vitro observations, deamination was slower for one CPD located at an intermediate rotational position compared with two other sites located at outside positions, and all were much faster than for CPDs at non-TCG sites. Photoproduct formation was also highly suppressed at one site, possibly due to its interaction with a histone tail. Thus, it was shown that CPDs of TCG sites deaminate the fastest in vivo and that nucleosomes can modulate both their formation and deamination, which could contribute to the UV mutation hot spots and cold spots. 相似文献
965.
966.
Xinqiong Huang Yujie Qian Hainan Wu Xiaoxue Xie Qin Zhou Ying Wang Weilu Kuang Lin Shen Kai Li Juan Su Liangfang Shen Xiang Chen 《The journal of histochemistry and cytochemistry》2015,63(2):88-98
Radiotherapy is the first-line treatment for all stages of cervical cancer, whether it is used for radical or palliative therapy. However, radioresistance of cervical cancer remains a major therapeutic problem. Consequently, we explored if E-cadherin (a marker of epithelial-mesenchymal transition) and osteopontin could predict radioresistance in patients with locally advanced cervical squamous cell carcinoma (LACSCC). Patients were retrospectively reviewed and 111 patients divided into two groups (radiation-resistant and radiation-sensitive groups) according to progression-free survival (PFS). In pretreated paraffin-embedded tissues, we evaluated E-cadherin and osteopontin expression using immunohistochemical staining. The percentage of patients with high osteopontin but low E-cadherin expression in the radiation-resistant group was significantly higher than those in the radiation-sensitive group (p<0.001). These patients also had a lower 5-year PFS rate (p<0.001). Our research suggests that high osteopontin but low E-cadherin expression can be considered as a negative, independent prognostic factor in patients with LACSCC ([Hazard ratios (95% CI) 6.766 (2.940, 15.572)], p<0.001). 相似文献
967.
Fangzhi Tan Cheng Qian Ke Tang Saber Mohamed Abd-Allah Naihe Jing 《The Journal of biological chemistry》2015,290(7):4500-4511
Mouse pluripotent stem cells (PSCs), such as ES cells and induced PSCs (iPSCs), are an excellent system to investigate the molecular and cellular mechanisms involved in early embryonic development. The signaling pathways orchestrated by leukemia inhibitor factor/STAT3, Wnt/β-catenin, and FGF/MEK/ERK play key roles in the generation of pluripotency. However, the function of TGF-β signaling in this process remains elusive. Here we show that inhibiting TGF-β signaling with its inhibitor SB431542 can substitute for Oct4 during reprogramming. Moreover, inhibiting TGF-β signaling can sustain the pluripotency of iPSCs and ES cells through modulating FGF/MEK/ERK signaling. Therefore, this study reveals a novel function of TGF-β signaling inhibition in the generation and maintenance of PSCs. 相似文献
968.
Qian Dong Sarah E. Ernst Lynda S. Ostedgaard Viral S. Shah Amanda R. Ver Heul Michael J. Welsh Christoph O. Randak 《The Journal of biological chemistry》2015,290(22):14140-14153
The ATP-binding cassette (ABC) transporter cystic fibrosis transmembrane conductance regulator (CFTR) and two other non-membrane-bound ABC proteins, Rad50 and a structural maintenance of chromosome (SMC) protein, exhibit adenylate kinase activity in the presence of physiologic concentrations of ATP and AMP or ADP (ATP + AMP ⇆ 2 ADP). The crystal structure of the nucleotide-binding domain of an SMC protein in complex with the adenylate kinase bisubstrate inhibitor P1,P5-di(adenosine-5′) pentaphosphate (Ap5A) suggests that AMP binds to the conserved Q-loop glutamine during the adenylate kinase reaction. Therefore, we hypothesized that mutating the corresponding residue in CFTR, Gln-1291, selectively disrupts adenylate kinase-dependent channel gating at physiologic nucleotide concentrations. We found that substituting Gln-1291 with bulky side-chain amino acids abolished the effects of Ap5A, AMP, and adenosine 5′-monophosphoramidate on CFTR channel function. 8-Azidoadenosine 5′-monophosphate photolabeling of the AMP-binding site and adenylate kinase activity were disrupted in Q1291F CFTR. The Gln-1291 mutations did not alter the potency of ATP at stimulating current or ATP-dependent gating when ATP was the only nucleotide present. However, when physiologic concentrations of ADP and AMP were added, adenylate kinase-deficient Q1291F channels opened significantly less than wild type. Consistent with this result, we found that Q1291F CFTR displayed significantly reduced Cl− channel function in well differentiated primary human airway epithelia. These results indicate that a highly conserved residue of an ABC transporter plays an important role in adenylate kinase-dependent CFTR gating. Furthermore, the results suggest that adenylate kinase activity is important for normal CFTR channel function in airway epithelia. 相似文献
969.
970.