全文获取类型
收费全文 | 1167篇 |
免费 | 73篇 |
专业分类
1240篇 |
出版年
2023年 | 7篇 |
2022年 | 18篇 |
2021年 | 31篇 |
2020年 | 18篇 |
2019年 | 20篇 |
2018年 | 24篇 |
2017年 | 34篇 |
2016年 | 44篇 |
2015年 | 49篇 |
2014年 | 57篇 |
2013年 | 84篇 |
2012年 | 93篇 |
2011年 | 84篇 |
2010年 | 46篇 |
2009年 | 44篇 |
2008年 | 55篇 |
2007年 | 61篇 |
2006年 | 49篇 |
2005年 | 60篇 |
2004年 | 43篇 |
2003年 | 54篇 |
2002年 | 43篇 |
2001年 | 10篇 |
2000年 | 10篇 |
1999年 | 9篇 |
1998年 | 10篇 |
1996年 | 5篇 |
1995年 | 7篇 |
1994年 | 4篇 |
1993年 | 7篇 |
1992年 | 6篇 |
1991年 | 4篇 |
1990年 | 4篇 |
1988年 | 5篇 |
1986年 | 4篇 |
1984年 | 5篇 |
1983年 | 4篇 |
1976年 | 4篇 |
1928年 | 3篇 |
1926年 | 4篇 |
1913年 | 8篇 |
1912年 | 5篇 |
1911年 | 3篇 |
1910年 | 3篇 |
1909年 | 4篇 |
1908年 | 6篇 |
1907年 | 4篇 |
1904年 | 7篇 |
1865年 | 5篇 |
1860年 | 3篇 |
排序方式: 共有1240条查询结果,搜索用时 0 毫秒
51.
52.
Grishko V Pastukh V Solodushko V Gillespie M Azuma J Schaffer S 《American journal of physiology. Heart and circulatory physiology》2003,285(6):H2364-H2372
Angiotensin II contributes to ventricular remodeling by promoting both cardiac hypertrophy and apoptosis; however, the mechanism underlying the latter phenomenon is poorly understood. One possibility that has been advanced is that angiotensin II activates NADPH oxidase, generating free radicals that trigger apoptosis. In apparent support of this notion, it was found that angiotensin II-mediated apoptosis in the cardiomyocyte is blocked by the NADPH oxidase inhibitor diphenylene iodonium. However, three lines of evidence suggest that peroxynitrite, rather than superoxide, is responsible for angiotensin II-mediated DNA damage and apoptosis. First, the inducible nitric oxide inhibitor aminoguanidine prevents angiotensin II-induced DNA damage and apoptosis. Second, based on ligation-mediated PCR, the pattern of angiotensin II-induced DNA damage resembles peroxynitritemediated damage rather than damage caused by either superoxide or nitric oxide. Third, angiotensin II activates p53 through the phosphorylation of Ser15 and Ser20, residues that are commonly phosphorylated in response to DNA damage. It is proposed that angiotensin II promotes the oxidation of DNA, which in turn activates p53 to mediate apoptosis. 相似文献
53.
54.
55.
56.
Guthaus E Bürgle M Schmiedeberg N Hocke S Eickler A Kramer MD Sweep CG Magdolen V Kessler H Schmitt M 《Biological chemistry》2002,383(1):207-216
The urokinase-type plasminogen activation system, including the serine protease uPA (urokinase-type plasminogen activator) and its cell surface receptor (uPAR, CD87), are important key molecules in tumor invasion and metastasis. Besides its proteolytic function, binding of uPA to uPAR on tumor cells exerts various cell responses such as migration, adhesion, proliferation, and differentiation. Hence, the uPA/uPAR system is a potential target for tumor therapy. We have designed a new generation of uPA-derived synthetic cyclic peptides suited to interfere with the binding of uPA to uPAR and present a new technology involving micro silica particles coated with uPA (SP-uPA) and reacting with recombinant soluble uPAR (suPAR), to rapidly assess the antagonistic potential of uPA-peptides by flow cytofluorometry (FACS). For this, we used silica particles of 10 microm in diameter to which HMW-uPA is coupled using the EDC/NHS method. Soluble, recombinant suPAR was added and the interaction of SP-uPA with suPAR verified by reaction with monoclonal antibody HD13.1 directed to uPAR, followed by a cyan dye (cy5)-labeled antibody directed against mouse IgG. Thereby it was possible to test naturally occurring ligands of uPAR (HMW-uPA, ATF) as well as highly effective, synthetic cyclic uPA-derived peptides (cyclo21,29[D-Cys21Cys29]-UPA21-30, cyclo21,29[D-Cys21Nle28Cys29]-uPA21-30, cyclo21,29[D-Cys(21)2-Nal24Cys29]-uPA21-30, and cyclo21,29[D-Cys21Orn23Thi24Thi25Cys29]-uPA21-30. The results obtained with the noncellular SP-uPA/uPAR system are highly comparable to those obtained with a cellular system involving FITC-uPA and the promyeloid cell line U937 as the source of uPAR. 相似文献
57.
In the present work, we measured survival and the platinum on the genome after treatment of repair-proficient or repair-deficient Escherichia coli strains with trans-[PtCl2(E-iminoether)2] and compared these results with the effects of “classical” cisplatin. We found that toxicity of antitumor trans-[PtCl2(E-iminoether)2] in repair-deficient trains was much less than that of cisplatin. This markedly reduced toxicity was not a consequence of the reduced uptake or low levels of DNA binding in the bacteria cells but rather appeared to reflect DNA binding mode of this trans-platinum drug different from that of cisplatin. 相似文献
58.
BACKGROUND: Traditionally, the bone maturity at birth has been estimated from the radiological presence and size of the ossified distal femoral epiphysis. This study was conducted in a search for a sonographic tool for the evaluation of neonatal bone maturity. METHODS: We examined sonographically 256 neonates within 24 h of birth. Gestational ages ranged from 36 to 42 weeks (mean: 39.4; median: 40). Birth weights ranged from 1,945 to 5,000 g (mean: 3,175; median: 3,180). The distal femoral epiphysis was imaged on the coronal plane sonogram of the distal femur with the knee at 90 degrees flexion and the distal femoral epiphysis maximal height was recorded. The acetabulum was imaged using Graf's method in the coronal plane image and the acetabular diameter recorded. RESULTS: It was found that plotting the distal femoral epiphysis against neonatal birth weight and gestational age provided a simple method for assessing the bone maturity. According to our study, a neonate can be regarded as bone maturity percentile X when plotting distal femoral epiphysis height or acetabulum diameter against birth weight and gestational age or when averaging the four readings. CONCLUSIONS: We suggest performing sonography of the distal femoral epiphysis as a bedside tool for the assessment of skeletal maturity in newborns. 相似文献
59.
60.
Fridman AS Brabec V Haroutiunian SG Wartell RM Lando DY 《Journal of biomolecular structure & dynamics》2003,20(4):533-545
DNA interstrand cross-links are usually formed due to bidentate covalent or coordination binding of a cross-linking agent to nucleotides of different strands. However interstrand linkages can be also caused by any type of chemical modification that gives rise to a strong local stabilization of the double helix. These stabilized sites conserve their helical structure and prevent local and total strand separation at temperatures above the melting of ordinary AT and GC base pairs. This local stabilization makes DNA melting fully reversible and independent of strand concentration like ordinary covalent interstrand cross-links. The stabilization can be caused by all the types of chemical modifications (interstrand cross-links, intrastrand cross-links or monofunctional adducts) if they give rise to a strong enough local stabilization of the double helix. Our calculation demonstrates that an increase in stability by 25 to 30 kcal in the free energy of a single base pair of the double helix is sufficient for this "cross-linking effect" (i.e. conserving the helicity of this base pair and preventing strand separation after melting of ordinary base pairs). For the situation where there is more then one stabilized site in a DNA duplex (e.g., 1 stabilized site per 1000 bp), a lower stabilization per site is sufficient for the "cross-linking effect" (18 - 20 kcal). A substantial increase in DNA stability was found in various experimental studies for some metal-based anti-tumor compounds. These compounds may give rise to the effect described above. If ligand induced stabilization is distributed among several neighboring base pairs, a much lower minimum increase per stabilized base pair is sufficient to produce the cross-linking effect (1 bp- 24.4 kcal; 5 bp- 5.3 kcal; 10 bp- 2.9 kcal, 25 bp- 1.4 kcal; 50 bp- 1.0 kcal). The relatively weak non-covalent binding of histones or protamines that cover long regions of DNA (20- 40 bp) can also cause this effect if the salt concentration of the solution is sufficiently low to cause strong local stabilization of the double helix. Stretches of GC pairs more than 25 bp in length inserted into poly(AT) DNA also exhibit properties of stabilizing interstrand cross-links. 相似文献