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81.
Metastasis is a major, life-threatening complication of cancer. The bloodstream is the most important disseminative route
for cancer cells liberated from their parent tumors. Single circulating cancer cells are arrested in the microvasculature,
where the vast majority are killed by rapid or slow processes, and the relatively few survivors grow into micrometastases.
We review the underlying causes of one type of rapid cancer cell death in the microcirculation, namely, that caused by biomechanical
interactions of cancer cells with microvessel walls, which may result in cell surface membrane expansion and lethal rupture.
These lethal interactions appear to be important rate-regulators in hematogenous metastasis, and to dictate some aspects of
metastatic patterns. Although these are not the only interactions involving cancer cells, in contrast to others involving
cellular and humoral defense mechanisms, they have received comparatively little attention. 相似文献
82.
Ras interaction with the GTPase-activating protein (GAP) 总被引:18,自引:0,他引:18
M D Schaber V M Garsky D Boylan W S Hill E M Scolnick M S Marshall I S Sigal J B Gibbs 《Proteins》1989,6(3):306-315
Biologically active forms of Ras complexed to GTP can bind to the GTPase-activating protein (GAP), which has been implicated as possible target of Ras in mammalian cells. In order to study the structural features of Ras required for this interaction, we have evaluated a series of mutant ras proteins for the ability to bind GAP and a series of Ras peptides for the ability to interfere with this interaction. Point mutations in the putative effector region of Ras (residues 32-40) that inhibit biological activity also impair Ras binding to GAP. An apparent exception is the Thr to Ser substitution at residue 35; [Ser-35]Ras binds to GAP as effectively as wild-type Ras even though this mutant is biologically weak in both mammalian and S. cerevisiae cells. In vitro, [Ser-35]Ras can also efficiently stimulate the S. cerevisiae target of Ras, adenylyl cyclase, indicating that other factors may influence Ras/protein interactions in vivo. Peptides having Ras residues 17-44 and 17-32 competed with the binding of Ras to E. coli-expressed GAP with IC50 values of 2.4 and 0.9 microM, respectively, whereas Ras peptide 17-26 was without effect up to 400 microM. A related peptide from the yeast GTP-binding protein YPT1 analogous to Ras peptide 17-32 competed with an IC50 value of 19 microM even though the YPT1 protein itself is unable to bind to GAP. These results suggest that determinants within Ras peptide 17-32 may be important for Ras binding to GAP. 相似文献
83.
Hiroaki Kataoka Kazuki Nabeshima Naoto Komada Masashi Koono 《Virchows Archiv. B, Cell pathology including molecular pathology》1989,57(1):157-165
Two new human cell lines, RCM-1 and CoCM-1, have been established from primary colorectal adenocarcinomas. Both cell lines
were unique in that the cultures secreted trypsin inhibitors in vitro. The activities of these inhibitors were accumulated
in serum-free media of both cell lines over a period of several days. Two inhibitors (PI-1 and PI-2) were isolated from serum-free
conditioned medium in which RCM-1 was grown by anion-exchange and gel filtration high-performance liquid chromatography. PI-1
inhibited trypsin and chymotrypsin strongly, and pancreatic elastase weakly. Its molecular weight was about 57 kilodaltons
(Kd) as determined by gel filtration chromatography. It cross-reacted with the antiserum elicited against human α1-antitrypsin in double immunodiffusion. PI-1 corresponding to α1
- antitrypsin was also demonstrated immunohistochemically in both cell lines. PI-2 inhibited trypsin strongly, and chymotrypsin,
kallikrein and plasmin weakly. It had higher molecular weight (200–300 Kd) than that of PI-1, and did not crossreact with
antisera against human α1-antitrypsin, α2-macroglobulin, α1-antichymotrypsin, α2-plasmin inhibitor, inter-α-trypsin inhibitor and urinary trypsin inhibitor. RCM-1 and CoCM-1 are the first colorectal adenocarcinoma
cell lines that secrete functionally active trypsin inhibitors, including α1-antitrypsin in vitro, and are useful for the study of tumor-cell derived proteinase inhibitors. 相似文献
84.
Teresa L. Johnson Mary Pat Moyer 《In vitro cellular & developmental biology. Plant》1990,26(11):1095-1100
Summary Normal human colon mucosa cells and cells obtained from histologically normal tissues near that cancer were fused with human
colon cancer cells. Resultant hybrid populations of normal and malignant cell fusions behaved as nonmalignant cells in culture,
were unable to grow in soft agar, did not express tumor-associated antigens, and were nontumorigenic in nude mice. Autofusion
of the cancer cell population led to a phenotype intermediate between normal and malignant cells. That is, the cultures had
a much lower plating efficiency in soft agar, and the tumors had a longer latency and slower growth rate in nude mice. This
is the first cell culture system to demonstrate that normal epithelial cells can suppress malignancy of their autologous cancer
cells, and is a prelude to more extensive studies of genetic events involved in malignant conversion of human colonic epithelium.
This study was supported by The University of Texas Health Science Center at San Antonio Center for Human Cell Biotechnology
and a graduate student stipend (T. J.) from the Department of Cellular and Structural Biology. 相似文献
85.
Atmospheric CO2 concentration has increased by 25% over the preindustrial level. A parallel increase in C concentration and decreases in N
concentration and δ13C of plants grown throughout this century have been observed in plant specimens stored in herbaria. We tested our previous
results in a study of 12 more species collected in the western Mediterranean throughout this century (1920–1930, 1945–1955,
and 1985–1990) and tree rings of Quercus pubescens from the same area. These changes were accompanied by apparent increases in condensed tannin concentration. A decreasing trend
in δ15N both in herbarium material and tree rings was also found, indicating that ecosystems might cope with higher plant N demand
by decreasing N losses and increasing N fixation and mineralization. These results may contribute to a better understanding
of the effects of global change on carbon and nitrogen cycling.
Received: 12 November 1995 / Accepted: 17 May 1996 相似文献
86.
Lymphocyte subpopulations of regional lymph nodes in human colon and gastric adenocarcinomas 总被引:3,自引:0,他引:3
Beatriz Lores-Vazquez Margarita Pacheco-Carracedo Josefina Oliver-Morales Purificación Parada-Gonzalez F. Gambón-Deza 《Cancer immunology, immunotherapy : CII》1996,42(6):339-342
In order to study the host immune response to tumours, previous knowledge of the cellular composition of regional draining
lymph nodes is necessary. Enlarged regional lymph nodes are a common finding in colon and gastric adenocarcinomas. We have
studied the cellular composition of normal non-reactive and of regional draining lymph nodes of colon and gastric adenocarcinomas.
In normal non-reactive lymph nodes, T lymphocytes (CD2+, CD7+) constituted the largest fraction of the lymphoreticular cells. These lymphocytes were mainly CD4+, and there were more cells expressing the CD45RA isoform of the CD45 antigen than CD45RO. Reactive lymph nodes presented
a decreased proportion of CD4+ CD45RA+ cells and an increased number of B cells. Although most of the T cells in the reactive nodes were CD4+ CD45RO+, their proportion was similar to that found in normal non-reactive nodes. We studied the presence of the molecules CD28 and
CD80 involved in the processes of interaction and activation of T and B lymphocytes. The CD28 molecule was found in all the
T lymphocytes, while the CD80 molecule was weakly expressed on the B lymphocyte membrane.
Received: 4 January 1996 / Accepted: 28 May 1996 相似文献
87.
Effects of interleukin-12 on in vitro culture with interleukin-2 of regional lymph node lymphocytes from lung cancer patients 总被引:2,自引:0,他引:2
T. Hanagiri Mitsuhiro Takenoyama Takashi Yoshimatsu Chikashi Hirashima Ichiro Yoshino Kozo Nakanishi Akira Nagashima Kikuo Nomoto Kosei Yasumoto 《Cancer immunology, immunotherapy : CII》1996,43(2):87-93
In the present study, we carried out a functional analysis of regional lymph node lymphocytes (RLNL) from patients with lung
cancer after in vitro activation by interleukin-2 (IL-2) and interleukin-12 (IL-12). IL-12 (100 U/ml) enhanced both the proliferation
and cytotoxic activity of RLNL in a culture with low doses of IL-2 (5 – 10 JRU/ml). After comparing an RLNL culture with a
low dose of IL-2 alone, a higher proportion of CD8+ cells and CD56+ cells and a lower proportion of CD4+ cells were found in the culture with both IL-12 and a low dose of IL-2. Such a combination of the cytokines effectively activated
RLNL in terms of the expression of IL-2 receptors. In the culture condition of IL-12 and a low dose of IL-2, a synergistic
effect was observed in the production of such cytokines as interferon γ, tumor necrosis factor α (TNFα), and TNFβ, as well
as in tumor cytotoxicity. However, the addition of IL-12 inhibited the cytotoxicity of RLNL in the culture with a high dose
of IL-2 (100 JRU/ml). This inhibition is considered to be partially due to the endogenous production of TNFα by lymphocytes,
because the neutralization of TNFα bioactivity partially restored the cytotoxic activities of RLNL. Furthermore, in the presence
of hydrocortisone, IL-12 synergistically enhanced the cytotoxic activity of RLNL cultured with a high dose of IL-2. These
results provide useful information about the improvement of adoptive immunotherapy against cancer using RLNL.
Received: 2 February 1996 / Accepted: 30 July 1996 相似文献
88.
Elizabeth A. Kingsley Teresa E. Carter Kevin D. Barrow Pamela J. Russell 《Cancer immunology, immunotherapy : CII》1996,41(6):348-354
A monoclonal antibody, BLCA-8, was raised against the human bladder cancer cell line, UCRU-BL-17CL. By flow cytometry and immunoperoxidase staining, this antibody was found to possess high specificity for bladder tumours, some reactivity with fetal tissues, and no reactivity with normal bladder, or any normal or malignant tissue. This high specificity and the stability of the antigen to the urinary environment suggest that BLCA-8 may have potential for use as an anti-bladder-cancer therapeutic agent. By thin-layer chromatography and autoradiography, BLCA-8 was found to bind four components within the neutral lipid fraction of a bladder cancer cell line, UCRU-BL-17/23. These components hadR
F values of 0.22, 0.16/0.15 (doublet), 0.12 and 0.08, and migrated below globoside, indicating the presence of more than four sugars. By enzyme-linked immunosorbant assay and thin-layer chromatography it was found that the binding of BLCA-8 to the lipid extract was increased by both mild alkaline hydrolysis and enzymatic treatments, indicating that adjacent phospholipids and glycolipids interfere with the accessibility of the antibody-binding site. Full biochemical characterisation of the BLCA-8 antigen is currently underway. 相似文献
89.
Humoral anti-idiotypic and anti-anti-idiotypic immune response in cancer patients treated with monoclonal antibody 17-1A 总被引:4,自引:0,他引:4
Peter Ragnhammar Maria Liljefors Anna-Lena Hjelm Håkan Mellstedt Jan-Erik Frödin J. Fagersberg 《Cancer immunology, immunotherapy : CII》1996,42(2):81-87
A group of 96 patients with advanced colorectal carcinoma were treated with the mouse (m) or chimeric (c) (mouse variable
regions × human IgG1 constant regions) monoclonal antibody (mAb) 17-1A recognizing the tumour-associated antigen GA733-2.
Eighty-two of the 83 patients treated with mmAb17-1A and 69% of the patients given cmAb17-1A (n = 13) developed anti-idiotypic antibodies (ab2). Auto-antibodies binding to tumour cells expressing GA733-2 were found in 7% of the patients. In a further 38 patients (40%)
antitumour-cell antibodies, i.e. anti-anti-idiotypic antibodies (ab3), were induced by the mAb17-1A therapy. Patients with detectable ab3 after treatment had significantly higher ab2 levels than those not developing ab3. Addition of granulocyte/macrophage-colony-stimulating factor (GM-CSF) to mmAb17-1A significantly enhanced the induction
of ab2 as well as induction of anti-anti-idiotypic antibodies (ab3), compared to mmAb17-1A alone. Patients with a high increase in antitumour-cell antibodies (ab3) induced by the therapy lived significantly longer than patients with no or a low level of induction of ab3 (P = 0.016). The results indicate that induction of an idiotypic network response might be an important effector mechanism in
mAb therapy.
Received: 20 October 1995 / Accepted: 18 December 1995 相似文献
90.
Yuichi Murayama Ryozaburo Mukai Tetsutaro Sata Satoko Matsunaga Atsuo Noguchi Yasuhiro Yoshikawa 《Microbiology and immunology》1996,40(6):467-471
In contrast to the case of peripheral T cells, the surface expression of CD20 antigen and the expression of CD20 mRNA in monkey lymph node (LN) T cells underwent a noticeable increase when they were cultured with mitogen and interleukin-2 (IL-2). To confirm in vivo regulation of CD20 expression during the activation of LN T cells, we examined LNs derived from monkeys experimentally inoculated with simian immunodeficiency virus (SIV). Significant expression of CD20 antigen was detected in the T cells of the LNs at the stage of lymphadenopathy. These findings suggest that lymphocyte activation in the LNs induced expression of the CD20 molecule in some T cells. 相似文献