全文获取类型
收费全文 | 52985篇 |
免费 | 5227篇 |
国内免费 | 1591篇 |
专业分类
59803篇 |
出版年
2024年 | 217篇 |
2023年 | 1111篇 |
2022年 | 1586篇 |
2021年 | 2461篇 |
2020年 | 2644篇 |
2019年 | 3528篇 |
2018年 | 2608篇 |
2017年 | 1796篇 |
2016年 | 1688篇 |
2015年 | 2156篇 |
2014年 | 3486篇 |
2013年 | 3895篇 |
2012年 | 2013篇 |
2011年 | 2639篇 |
2010年 | 1694篇 |
2009年 | 2191篇 |
2008年 | 2288篇 |
2007年 | 2263篇 |
2006年 | 2179篇 |
2005年 | 1817篇 |
2004年 | 1576篇 |
2003年 | 1323篇 |
2002年 | 1120篇 |
2001年 | 812篇 |
2000年 | 765篇 |
1999年 | 598篇 |
1998年 | 673篇 |
1997年 | 615篇 |
1996年 | 640篇 |
1995年 | 636篇 |
1994年 | 610篇 |
1993年 | 532篇 |
1992年 | 571篇 |
1991年 | 501篇 |
1990年 | 456篇 |
1989年 | 416篇 |
1988年 | 370篇 |
1987年 | 366篇 |
1986年 | 299篇 |
1985年 | 372篇 |
1984年 | 355篇 |
1983年 | 207篇 |
1982年 | 327篇 |
1981年 | 274篇 |
1980年 | 226篇 |
1979年 | 186篇 |
1978年 | 118篇 |
1977年 | 118篇 |
1976年 | 117篇 |
1973年 | 87篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
11.
Comment on: Rokavec M, et al. Mol Cell 2012; 45:777-89. 相似文献
12.
《Cell》2021,184(26):6281-6298.e23
13.
S20Y murine neuroblastoma cells appear to express a protein component(s) able to adhere specifically to the oligosaccharide portion of GM1 (oligo-GM1). To identify proteins with which the oligo-GM1 becomes closely associated, a radiolabeled (125I), photoactivatable derivative of oligo-GM1 was prepared. This was accomplished by reductive amination of the glucosyl moiety of oligo-GM1 to 1-deoxy-1-aminoglucitol, followed by reaction of the amine with sulfosuccinimidyl 2-(p-azidosalicylamido)ethyl-1,3'-dithiopropionate (SASD). Crosslinking studies using the photoactivatable probe indicated that it came in close proximity to a protein with an apparent molecular mass of approximately 71 kDa. In competition experiments, as little as a 10-fold molar excess of oligo-GM1 resulted in a selective reduction in labeling of this protein; preincubation with a 200-fold molar excess of siayllactose was necessary to observe the same change in the labeling pattern, lending additional support to the hypothesis that the approximately 71-kDa protein specifically associates with oligo-GM1. Cell surface location of the oligo-GM1 binding protein was confirmed using subcellular fractionation and morphological analyses. 相似文献
14.
15.
Hyun I. Park 《Analytical biochemistry》2010,396(2):262-60
Matrix metalloproteinases (MMPs) are a family of hydrolytic enzymes that play significant roles in development, morphogenesis, inflammation, and cancer invasion. Endometase (matrilysin 2 or MMP-26) is a putative early biomarker for human carcinomas. The effects of the ionic and nonionic detergents on catalytic activity of endometase were investigated. The hydrolytic activity of endometase was detergent concentration dependent, exhibiting a bell-shaped curve with its maximum activity near the critical micelle concentration (CMC) of nonionic detergents tested. The effect of Brij-35 on human gelatinase B (MMP-9), matrilysin (MMP-7), and membrane-type 1 MMP (MT1-MMP) was further explored. Their maximum catalysis was observed near the CMC of Brij-35 (∼ 90 μM). Their IC50 values were above the CMC. The inhibition mechanism of MMP-7, MMP-9, and MT1-MMP by Brij-35 was a mixed type as determined by Dixon’s plot; however, the inhibition mechanism of endometase was noncompetitive with a Ki value of 240 μM. The catalytic activities of MMPs are influenced by detergents. Monomer of detergents may activate and stabilize MMPs to enhance catalysis, but micelle of detergents may sequester enzyme and block the substrate binding site to impede catalysis. Under physiological conditions, a lipid or membrane microenvironment may regulate enzymatic activity. 相似文献
16.
17.
18.
We have established a series of 20 colorectal cancer cell lines and performed cytogenetic and RFLP analyses to show that the
recurrent genetic abnormalities of chromosomes 1, 5, 17 and 18 associated with multistep tumorigenesis in colorectal cancer,
and frequently detected as recurrent abnormalities in primary tumours, are also retained in long-term established cell lines.
Earlier studies by us and other investigators showed that allelic losses of chromosomes 1 and 17 in primary colorectal cancers
predicted poorer survival for the patients (P = 0.03). We utilized the cell lines to identify specific chromosomal sites or gene(s) on chromosomes 1 and 17 which confer
more aggressive phenotype. Cytogenetic deletions of chromosome 1p were detected in 14 out of the 20 (70%) cell lines, whereas
allelic deletions for 1p using polymorphic markers were detected in 13 out of 18 (72%) informative cell lines for at least
one polymorphic marker. We have performed Northern blotting, immunohistochemical staining (p53 mRNA, protein) and RFLP analysis
using several probes including p53 and nm23. RFLP analysis using a total of seven polymorphic markers located on 17p and 17q
arms showed allelic losses aroundthe p53 locus in 16 out of the 20 cell lines (80%), four of which were losses of thep53 locus itself. In addition, seven cell lines (out of nine informative cases) also showed losses of thenm23 gene, four with concurrent losses of thep53 locus, while the remaining three were homozygous. In addition, five out of seven cell lines withnm23 deletions were derived from hepatic metastatic tumours, and one cell line was obtained from recurrent tumour. A comparison
between allelic deletions of 1p and functional loss ofnm23 gene revealed a close association between these two events in cell lines derived from hepatic metastasis. Following immunohistochemical
staining, nine out of the twenty cell lines showed high levels (25–80%) of mutant p53, four showed intermediate levels (>20%),
and seven had undetectable levels of the protein. Of these seven, four showed complete absence of mRNA. Of the remaining three
cell lines one showed aberrant mRNA due to germline rearrangement of thep53 gene, whereas in two cell lines normal levels of mRNA were present. Nineteen of the 20 cell lines had normal germline configurations
for thep53 gene, while one showed a rearrangement. These data suggest that functional loss ofp53 andnm23 genes accomplished by a variety of mechanisms may be associated with poor prognosis and survival. In addition, concurrent
deletions of chromosome regions 17p, 17q and 1p were closely associated with high-stage hepatic metastatic disease. These
cell lines with well-characterized genetic alterations and known clinical history provide an invaluable source of material
for various biological and clinical studies relating to multistep colorectal tumorigenesis. 相似文献
19.
K. Sasikala Ch.V. Ramana P. Raghuveer Rao M. Subrahmanyam 《FEMS microbiology letters》1990,72(1-2):23-28
Abstract Photoproduction of hydrogen, nitrogenase activity (acetylene reduction) and hydrogenase activity (methylene blue dye reduction) were studied in free and alginate immobilized whole cells of a purple non-sulfur photosynthetic bacterium Rhodobacter sphaeroides O.U. 001. Four-fold increase in hydrogen production, two-fold increase in nitrogenase activity and 1.2-fold increase in the hydrogenase activity were observed in immobilized cells compared to free cells. Effect of various inhibitors (CO and C2 H2 ) and electron donor (H2 ) on the above three functions by free and immobilized cells has also been studied. 相似文献
20.
The morphology of dissociated single cerebellar Purkinje cells obtained from wild-type P1 CD1 mice was assessed in the absence
and in the presence of glia. A dedicated noninvasive technique based on optical microscopy was developed. Image processing
algorithms were implemented to extract metrical features characterizing cell structure and dendritic arborization. The morphological
features were analyzed in order to identify quantitative differences in Purkinje cell morphology due to interactions with
astrocytes. 相似文献