全文获取类型
收费全文 | 1407篇 |
免费 | 89篇 |
国内免费 | 48篇 |
出版年
2024年 | 3篇 |
2023年 | 15篇 |
2022年 | 31篇 |
2021年 | 37篇 |
2020年 | 42篇 |
2019年 | 49篇 |
2018年 | 42篇 |
2017年 | 31篇 |
2016年 | 30篇 |
2015年 | 52篇 |
2014年 | 110篇 |
2013年 | 110篇 |
2012年 | 61篇 |
2011年 | 94篇 |
2010年 | 59篇 |
2009年 | 73篇 |
2008年 | 86篇 |
2007年 | 79篇 |
2006年 | 63篇 |
2005年 | 69篇 |
2004年 | 63篇 |
2003年 | 55篇 |
2002年 | 49篇 |
2001年 | 25篇 |
2000年 | 18篇 |
1999年 | 16篇 |
1998年 | 12篇 |
1997年 | 17篇 |
1996年 | 13篇 |
1995年 | 18篇 |
1994年 | 15篇 |
1993年 | 12篇 |
1992年 | 8篇 |
1991年 | 4篇 |
1990年 | 7篇 |
1989年 | 8篇 |
1988年 | 7篇 |
1987年 | 3篇 |
1986年 | 3篇 |
1985年 | 5篇 |
1984年 | 10篇 |
1983年 | 6篇 |
1982年 | 8篇 |
1981年 | 7篇 |
1980年 | 5篇 |
1979年 | 4篇 |
1976年 | 2篇 |
1975年 | 2篇 |
1974年 | 2篇 |
1973年 | 2篇 |
排序方式: 共有1544条查询结果,搜索用时 15 毫秒
1.
《Journal of molecular biology》2021,433(21):167226
Many of the world's most important food crops such as rice, barley and maize accumulate silicon (Si) to high levels, resulting in better plant growth and crop yields. The first step in Si accumulation is the uptake of silicic acid by the roots, a process mediated by the structurally uncharacterised NIP subfamily of aquaporins, also named metalloid porins. Here, we present the X-ray crystal structure of the archetypal NIP family member from Oryza sativa (OsNIP2;1). The OsNIP2;1 channel is closed in the crystal structure by the cytoplasmic loop D, which is known to regulate channel opening in classical plant aquaporins. The structure further reveals a novel, five-residue extracellular selectivity filter with a large diameter. Unbiased molecular dynamics simulations show a rapid opening of the channel and visualise how silicic acid interacts with the selectivity filter prior to transmembrane diffusion. Our results will enable detailed structure–function studies of metalloid porins, including the basis of their substrate selectivity. 相似文献
2.
3.
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
4.
Distribution of neurons in the major pelvic ganglion of the rat which supply the bladder,colon or penis 总被引:2,自引:0,他引:2
Summary In male rats a large number of the postganglionic neurons which innervate the pelvic organs are located in the major pelvic ganglion. In the present study we have identified the location within this ganglion of neurons which project to either of three pelvic organs, the penis, colon or urinary bladder. Two fluorescent retrogradely-transported dyes, Fast Blue and Fluoro-Gold, were used. For most animals one dye was injected into the cavernous space of the penis, the wall of the distal colon or the wall of the urinary bladder. In a small number of animals two organs were injected, each with a different dye. One to six weeks after injection the major pelvic ganglia were fixed in buffered formaldehyde. The distribution of fluorescent dye-labelled cells was observed in whole mounts of complete ganglia and, in most cases, also in small accessory ganglia located between the ureter and the prostate. The studies showed a unique pattern of distribution for each organ-specific group of neurons. Most of the colon neurons are located in the major pelvic ganglion near the entrance of the pelvic nerve, whereas almost all of the penis neurons are near or within the penile nerve. Bladder neurons are relatively evenly distributed throughout the ganglion. These results demonstrate a distinct topographical organization of organ-specific neurons of the major pelvic ganglion of the male rat, a phenomenon which has also been observed in other peripheral ganglia. 相似文献
5.
Masanori Ito Kazuhiro Yoshida Eikai Kyo Ayse Ayhan Hirofumi Nakayama Wataru Yasui Hisao Ito Eiichi Tahara 《Virchows Archiv. B, Cell pathology including molecular pathology》1990,59(1):173-178
We have examined the expression of mRNAs for epidermal growth factor (EGF), transforming growth factor-alpha (TGF-α), EGF
receptor (EGFR), PDGF-A chain (PDGFA), PDGF-B chain (PDGFB) and PDGF receptor (PDGFR) genes in seven human colorectal carcinoma
cell lines and 18 human colorectal carcinomas.
In surgically resected specimens of the 18 colorectal tumors, TGF-α, EGFR, PDGFA, PDGFB and PDGFR mRNAs were detected at various
levels in 15 (83%), 9 (50%), 18 (100%), 8 (44%) and 12 (67%), respectively. They were also detected in normal tissues. Interestingly,
EGF mRNA was detected in only five (28%) of the tumors, but not in normal mucosa. Expression of EGF was also confirmed immunohistochemically
in tumor cells. Of the five tumors expressing EGF, four expressed EGFR mRNA and showed a tendency to invade veins and lymphatics.
All the colorectal carcinoma cell lines expressed TGF-α mRNA, and five cell lines expressed EGFR mRNA simultaneously. Production
of TGF-α protein by DLD-1 and CoLo320DM cells was confirmed by TGF-α specific monoclonal antibody binding assay. The spontaneous3H-thymidine uptake by DLD-1 was suppressed by an anti-TGF-α monoclonal antibody. PDGFA and PDGFB mRNA were also expressed
in four cell lines, but PDGFR and EGF mRNA was not detected. These results suggest that human colorectal carcinomas express
multi-loops of growth factors and that TGF-α produced by tumor cells functions as an autocrine growth factor in human colonic
carcinoma. 相似文献
6.
Øyvind Skraastad Karl L. Reichelt 《Virchows Archiv. B, Cell pathology including molecular pathology》1988,56(1):321-325
Previous work indicates that the colonic epithelial cell proliferation in mice is reversibly inhibited by the tripeptide pGlu-His-GlyOH
found in aqueous extracts of the intestine. In the present study we examined the possible tissue specificity of the colon
mitosis inhibitor. The mitotic rate in the small intestine, epidermis and forestomach in mice was registered after a single
i.p. injection of the tripeptide. A significantly reduced rate of cell renewal was found at 18 h in the epidermis whereas
no inhibition was observed in the forestomach or ileal epithelium. To investigate whether the amino acid sequence of the tripeptide
is essential for the inhibitory effect, three structurally related bioactive peptides were tested and compared to the effect
of CMI. CMI showed a bell-shaped dose-response relationship as previously shown, whereas the mitotic rate was not reduced
in the colonie epithelium after treatment with either an epidermal mitosis inhibitory pentapeptide, or the dipeptide pGlu-GlyOH,
or an analogue of luteinizing hormone-releasing hormone. The efficacy of the tripeptide was dependent on the basal rate of
cell renewal in the colonie epithelium. When the tripeptide was given at the circadian nadir of cell proliferation a delayed
reduction of the proliferative activity was observed at 6 h after treatment, whereas treatment when the rate of cell proliferation
was at its circadian zenith gave an immediate mitotic inhibition. 相似文献
7.
Shin-Ichi Hayama Rika Akamatsu Mayumi Kishimoto Masatsugu Suzuki Hideo Nigi 《Primates; journal of primatology》1988,29(3):423-426
Diverticular disease of the colon was detected in a female Japanese monkey by X-ray examination. The monkey was 15 years old
and had been kept under captive conditions for nine years. Lack of appetite and activity, and constipation were observed.
The monkey was given fiber-rich vegetables and wild plants, and its appetite and activity then improved. Based on a consideration
of various factors, it is suggested that one possible cause of the diverticulosis in this case was a low dietary fiber intake. 相似文献
8.
Immunotargeting of daunomycin to localized and metastatic human colon adenocarcinoma in athymic mice
Esther Hurwitz Ruth Adler Daniel Shouval Hiroshi Takahashi Jack R. Wands Michael Sela 《Cancer immunology, immunotherapy : CII》1992,35(3):186-192
Summary A monoclonal antibody (designated SF25), which recognizes a protein antigen expressed on a large number of human colon carcinomas, was used for drug targeting. Daunomycin-antibody conjugates were prepared by two previously described procedures. In one, the drug was bound to the antibody through a spacer of small molecular mass (cis-aconitic acid), while in the other a dextran bridge served as the link between drug and antibody. High substitution rates of drug to antibody were obtained using the latter binding procedure. Both conjugates were tested in vitro against two human colon carcinoma cell lines, LS180 and KM-12. The efficacy of a daunomycin-dextran-SF25 antibody conjugate was tested against colon carcinoma LS180 tumors transplanted at different sites into athymic mice. The specific conjugate was significantly more inhibitory to a subcutaneous tumor growth than its components or their mixture. SF25 antibody alone showed antitumoral effects against all three forms of transplanted tumor tested, namely, local, metastatic or intrahepatic, whereas daunomycin, on its own, was effective only against the subcutaneous tumor. Binding of daunomycin to dextran partially improved its inhibitory activity against the metastatic tumor. The conjugate, daunomycin-dextran-SF25 antibody reduced the number of metastatic foci, increased the survival rate and delayed death. Yet against lymph node metastases it was not significantly better than a mixture of both constituents. However, results obtained with an intrahepatic tumor, a model that mimics the natural progression of the disease, resembled those described with the subcutaneous tumor. Daunomycin-dextran-SF25 antibody was significantly more effective than all components separately and than a mixture of drug and antibody, provided a highly drug-substituted conjugate was used. 相似文献
9.
Mui Keng Tan 《Plant molecular biology》1991,17(2):221-227
A total of 864 bases from 5 regions interspersed in the 18S and 26S rRNA molecules from various clones of Pteridium covering the general geographical distribution of the genus was analysed using a rapid rRNA sequencing technique. No base difference has been detected amongst the three major lineages, two of which apparently separated before the breakup of the ancient supercontinent, Pangaea. These regions of the rRNA sequences have thus been conserved for at least 160 million years and are here compared with other eukaryotic, especially plant rRNAs. 相似文献
10.
Summary Lens fibers are coupled by communicating junctions, clusters of cell-to-cell channels composed of a 28-kD intrinsic membrane protein (MIP26). Evidence suggests that these and other cell-to-cell channels may close as a result of protein conformational change induced by activated calmodulin. To test the validity of this hypothesis, we have measured the intrinsic fluorescence emission and far-ultraviolet circular dichroism of the isolated components MIP26, calmodulin, and the MIP26-calmodulin complex, both in the absence and presence of Ca++, an uncoupling agent. MIP26 shows no change in either, fluorescence emission (primarily tryptophan and a measure of aromatic constitutivity) or in its circular dichroism spectrum. Calmodulin exhibits a 32% increase in fluorescence emission intensity with constant emission wavelength, entirely tyrosine, and a 44% increase in -helicity, changes previously described. The MIP26-calmodulin complex, on the other hand, displays fluorescence emission and circular dichroism spectra which are slightly different from the sum of the two single components, but shows marked differences in both spectra upon Ca++ addition. This indicates a change in conformation in one or both of the two components. Spectral changes include a 5-nm blue-shift, a 50% increase in tyrosine fluorescene emission, a 25% decrease in tryptophan fluorescence emission, and a 5% increase in the -helicity of the complex. These changes also occur about an isosbestic point and are fully reversible. These data provide additional evidence that activated calmodulin may modulate gating of cell-to-cell channels by affecting channel protein. 相似文献