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121.
122.
Daisuke Abe Toshiyuki Sakaki Tatsuya Kusudo Atsushi Kittaka Nozomi Saito Yoshitomo Suhara Toshie Fujishima Hiroaki Takayama Hiromi Hamamoto Masaki Kamakura Miho Ohta Kuniyo Inouye 《Drug metabolism and disposition》2005,33(6):778-784
Recently, we demonstrated that some A-ring-modified vitamin D3 analogs had unique biological activity. Of these analogs, 2alpha-propoxy-1alpha,25(OH)2D3 (C3O1) and 2alpha-(3-hydroxypropoxy)-1alpha,25(OH)2D3 (O2C3) were examined for metabolism by CYP27A1 and CYP24A1. Surprisingly, CYP27A1 catalyzed the conversion from C3O1 to O2C3, which has 3 times more affinity for vitamin D receptor than C3O1. Thus, the conversion from C3O1 to O2C3 by CYP27A1 is considered to be a metabolic activation process. Five metabolites were detected in the metabolism of C3O1 and O2C3 by human CYP24A1 including both C-23 and C-24 oxidation pathways. On the other hand, three metabolites of the C-24 oxidation pathway were detected in their metabolism by rat CYP24A1, indicating a species-based difference in the CYP24A1-dependent metabolism of C3O1 and O2C3 between humans and rats. Kinetic analysis revealed that the Km and kcat values of human CYP24A1 for O2C3 are, respectively, approximately 16 times more and 3 times less than those for 1alpha,25(OH)2D3. Thus, the catalytic efficiency, kcat/Km, of human CYP24A1 for O2C3 is only 2% of 1alpha,25(OH)2D3. These results and a high calcium effect of C3O1 and O2C3 in animal experiments using rats suggest that C3O1 and O2C3 are promising for clinical treatment of osteoporosis. 相似文献
123.
Recent studies have shown that apoptosis plays an important role in vascular remodeling. We examined central nervous system vascular malformations for the presence of DNA fragmentation which is the evidence of apoptosis. We hypothesize that vascular remodeling through apoptosis may be responsible for recurrence or hemorrhage in these lesions. We examined the specimens of central nervous system vascular malformations by in situ end labeling (ISEL) of fragmented DNA. Moreover, we examined the expression of Caspase-3 which is apoptosis-related proteins in these lesions by immunohistochemistry. DNA fragmentation was observed in all 15 arteriovenous malformation (AVM) specimens. ISEL-positive cells were mainly distributed in the endothelium, media and perivascular tissue. In cavernous hemangioma (CH), DNA fragmentation was also observed in all 5 specimens. ISEL-positive cells were distributed in the endothelium, subendothelium and intercavernous matrix. Thirteen out of 15 AVM lesions stained positive for Caspase-3. Caspase-3 immunoreactivity was mainly distributed in the endothelium, media and perivascular tissue. This distribution was similar to that of ISEL positive cells. As for CHs, all 5 lesions stained positive for Caspase-3. Caspase-3 immunoreactivity was distributed in the endothelium, subendothelium and intercavernous matrix. Our findings indicate that apoptotic cell death and vascular remodeling play a role in the development and maintenance of vascular malformations. 相似文献
124.
Wang L Kuroiwa Y Kamitani T Li M Takahashi T Suzuki Y Shimamura M Hasegawa O 《Journal of neurology》2000,247(5):356-363
To determine whether there are characteristic changes in event-related potentials (ERPs) in parkinsonian syndromes we studied
8 patients with progressive supranuclear palsy (PSP), 10 patients with corticobasal degeneration (CBD), 9 patients with striatonigral
degeneration (SND), and 16 patients with idiopathic Parkinson's disease (PD) with a mean duration of illness shorter than
5 years in each group. A visual oddball paradigm was employed to elicit P300. P300 to the rare target and rare nontarget stimuli
and reaction time (RT) to rare target stimuli in each group were compared with those in the corresponding age-matched normal
control group and to each other after age correction. The correlation of P300 and RT to motor disability score was also studied.
In PSP P300 amplitude was markedly reduced while in CBD P300 latency was prolonged. P300 amplitude to rare nontargets in SND
and PD was attenuated. The mean RT in the PSP and the CBD group was significantly longer than in the other two groups. The
mean RT in PD and P300 amplitude to rare nontargets in both CBD and PD showed significant correlation with the severity of
motor disability. Simultaneous measurement of P300 and RT may yield useful supplementary information in facilitating diagnosis
of parkinsonian syndromes in addition to clinical criteria.
Received: 6 April 1999, Received in revised form: 5 August 1999, Accepted: 12 January 2000 相似文献
125.
Masakatsu Fujinoki Tatsuya Suzuki Takeshi Takayama Hiroaki Shibahara Hideki Ohtake 《Reproductive Medicine and Biology》2006,5(2):123-135
Background and Aims It has been widely accepted that sperm hyperactivation is regulated by protein phosphorylations. But, the sperm hyperactivation
phosphorylation pathway is not well understood yet because several different proteins have been detected in other studies.
In order to understand the phosphorylation pathway that regulates hyperactivation, we established how to extract sperm protein
completely and detected proteins that were phosphorylated during hyperactivation.
Methods Protein phosphorylation of hamster spermatozoa was detected by western blotting using antiphospho-amino acid monoclonal antibodies
or the SELDI ProteinChip system with IMAC-Ga(III).
Results We detected 75 protein/peptide phosphoryations using the method established in the present study. Tyrosine phosphorylations
occurred during hyperactivation. Serine or threonine phosphorylations occurred for 30 min. Furthermore, four of the serine
or threonine phosphorations were phosphorylated by A-kinase. As for peptides, 15 peptides were dephosphorylated for 30 min.
Other peptides were phosphorylated during hyperactivation.
Conclusions Because most of the proteins detected in the present study have been described previously, we could detect comprehensive protein
phosphorylations. Moreover, we also detected many novel phosphopeptides. Although we did not understand the role of peptide,
it was likely that motility was basically regulated by serine/threonine phosphorylations and hyperactivation was mainly regulated
by tyrosine phosphorylations. (Reprod Med Biol 2006; 5: 123–135) 相似文献
126.
N Sakamoto S Kokura T Okuda T Hattori K Katada Y Isozaki N Nakabe O Handa T Takagi T Ishikawa Y Naito N Yoshida T Yoshikawa 《International journal of hyperthermia》2005,21(7):603-614
AIM: The aim of the present study was to explore whether heme oxygenase-1 (HO-1) is involved in the hyperthermia-provided protection of the small intestine from ischemia/reperfusion injury in rats. METHODS: Intestinal damage was induced in male Sprague-Dawley rats by clamping both the superior mesenteric artery and the celiac trunk for 30 min, followed by reperfusion. Whole-body hyperthermia was induced in anesthetized rats by placement in a temperature-controlled water bath. Whole-body hyperthermia to a core temperature of 42-43 degrees C for 15 min was followed by passive cooling. We started the hyperthermic treatment 6 h before the vascular clamping. The severity of the mucosal injury was evaluated by several biochemical markers and histological findings. Hyperthermia-induced heat-shock proteins were detected by Western blotting. We also investigated the effect of zinc protoporphyrin IX (an HO-1 inhibitor) on the protective effect of hyperthermia. RESULTS: The rats, which were killed after ischemia/reperfusion, had severe intestinal inflammation. Hyperthermia significantly induced the production of Hsp70 and HO-1 in intestinal mucosa and significantly reduced ischemia/reperfusion-induced mucosal injury. The combination of zinc protoporphyrin IX with hyperthermia extinguished the protective effects of hyperthermia on ischemia/reperfusion injury. CONCLUSION: Hyperthermia protects against ischemia/reperfusion injury in rat small intestine through the expression of heat-shock proteins, especially HO-1. 相似文献
127.
Construction of a natural product library containing secondary metabolites produced by actinomycetes
To construct a natural product library for drug screening, we isolated secondary metabolites from a wide variety of actinomycetes cultured from marine sponges. The results suggested that marine sponges are a promising source of actinomycetes with the potential to produce new metabolites. Furthermore, we evaluated the chemical space occupied by our natural product library (CB library) by multidimensional principal component analysis and compared it with a commercially available compound library (ZINC library), which was randomly selected from the ZINC library (approximately 30?000?000 compounds). The CB library occupied a wider chemical space than the ZINC library. Bioactive compounds in the CB library possessed a wide chemical space that was not covered by ZINC library. These results indicate that the CB library mainly comprises secondary metabolites from actinomycetes, and it has great potential as a source of compounds for drug screening. 相似文献
128.
Murakami M Kashiwakura I Hayase Y Takagi Y 《Biological & pharmaceutical bulletin》1999,22(11):1153-1157
We examined the effect of murine kidney extract (MKE) on the clonal growth of mast cells from murine peritoneal cells. Adding MKE resulted in a 40% inhibition of colony formation of mast cells in a methylcellulose culture, and a 90% decrease in mast cell numbers and histamine content in mast cells in a liquid culture containing stem cell factor and interleukin-3. The mast cell inhibitory factors in MKE were heat sensitive proteins of approximately 560 and 24 kDa. These results suggest that MKE contains regulators that suppress the growth of murine mast cells and histamine synthesis. 相似文献
129.
Amano S Mimura T Yamagami S Osakabe Y Miyata K 《Japanese journal of ophthalmology》2005,49(6):448-452
Purpose
To examine the properties of corneas tissue-engineered with cultured human corneal endothelial cells (HCEC) and human corneal stroma.Methods
Primary HCEC cultures were established from endothelial cell layer explants and propagated on culture dishes coated with bovine corneal endothelial extracellular matrix. A cell suspension of HCEC at the fifth passage was transferred onto human corneal stroma deprived of endothelial cells, and the corneas were gently centrifuged to enhance cell attachment. The cell density of the tissue-engineered corneas was examined after staining with alizarin red and trypan blue. The tissue-engineered corneas were histologically examined by light and electron microscopy. The pump function of the tissue-engineered corneas was measured using an Ussing chamber.Results
The mean endothelial cell density of four tissue-engineered corneas was 2380 ± 264 cells/mm2 (mean ± SD). HCEC on the tissue-engineered corneas had a morphology similar to HCEC in vivo. The pump function parameters of the tissue-engineered corneas were 55%–75% of those of normal corneas.Conclusions
HCEC on the tissue-engineered corneas have morphology and cellular density similar to HCEC in vivo, whereas the pump function of the tissue-engineered corneas was lower than in normal corneas. Jpn J Ophthalmol 2005;49:448–452 © Japanese Ophthalmological Society 2005 相似文献130.
Cetuximab delivery and antitumor effects are enhanced by mild hyperthermia in a xenograft mouse model of pancreatic cancer 下载免费PDF全文
Ryoichi Miyamoto Tatsuya Oda Shinji Hashimoto Tomohiro Kurokawa Yuki Inagaki Osamu Shimomura Yusuke Ohara Keiichi Yamada Yoshimasa Akashi Tsuyoshi Enomoto Mikio Kishimoto Hideto Yanagihara Eiji Kita Nobuhiro Ohkohchi 《Cancer science》2016,107(4):514-520
Even with current promising antitumor antibodies, their antitumor effects on stroma‐rich solid cancers have been insufficient. We used mild hyperthermia with the intent of improving drug delivery by breaking the stromal barrier. Here, we provide preclinical evidence of cetuximab + mild hyperthermia therapy. We used four in vivo pancreatic cancer xenograft mouse models with different stroma amounts (scarce, MIAPaCa‐2; moderate, BxPC‐3; and abundant, Capan‐1 and Ope‐xeno). Cetuximab (1 mg/kg) was given systemically, and the mouse leg tumors were concurrently heated using a water bath method for 30 min at three different temperatures, 25°C (control), 37°C (intra‐abdominal organ level), or 41°C (mild hyperthermia) (n = 4, each group). The evaluated variables were the antitumor effects, represented by tumor volume, and in vivo cetuximab accumulation, indirectly quantified by the immunohistochemical fluorescence intensity value/cell using antibodies against human IgG Fc. At 25°C, the antitumor effects were sufficient, with a cetuximab accumulation value (florescence intensity/cell) of 1632, in the MIAPaCa‐2 model, moderate (1063) in the BxPC‐3 model, and negative in the Capan‐1 and Ope‐xeno models (760, 461). By applying 37°C or 41°C heat, antitumor effects were enhanced shown in decreased tumor volumes. These enhanced effects were accompanied by boosted cetuximab accumulation, which increased by 2.8‐fold (2980, 3015) in the BxPC‐3 model, 2.5‐ or 4.8‐fold (1881, 3615) in the Capan‐1 model, and 3.2‐ or 4.2‐fold (1469, 1922) in the Ope‐xeno model, respectively. Cetuximab was effective in treating even stroma‐rich and k‐ras mutant pancreatic cancer mouse models when the drug delivery was improved by combination with mild hyperthermia. 相似文献